text:
Battle on Snowshoes
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For a less well-known skirmish in 1757, see Battle on Snowshoes (1757).
1758 Battle on Snowshoes
Part of the French and Indian War

A 1776 artist's rendition of Robert Rogers, whose likeness was never made from life
Date
March 23, 1758
Location
near Lake George, New York
Result
French victory
Belligerents
France Great Britain
Commanders and leaders
Ensign Joseph de la Durantaye
Ensign Jean-Baptiste de Langy Captain Robert Rogers
Strength
about 300[1] 181[2]
Casualties and losses
6 killed, 24 wounded (many of whom died of their wounds)[3] 144 killed
7 captured[3]
[hide]
v
t
e
Seven Years' War in North America: The French and Indian War, St. Lawrence and Mohawk theater
Lake George
Fort Bull
Fort Oswego
1st Snowshoes
Sabbath Day Point
Fort William Henry
German Flatts
2nd Snowshoes
Fort Carillon
Fort Frontenac
La Belle-Famille
Fort Niagara
Fort Ticonderoga
Beauport
Quebec
St. Francis
Sainte-Foy
Neuville
Thousand Islands
Detail from a 1777 map by John Montresor. In 1758, the road along the left side of Lake George did not exist. Forts Edward and William Henry are near the bottom of this map. This battle probably took place somewhere west of the hills near Sabbathday Point.
The 1758 Battle on Snowshoes occurred on March 13, 1758, during the French and Indian War. It was fought by members of British Ranger companies led by Robert Rogers against French troops and Indians allied to France. The battle took place near Lake George, now in northern New York, but then in the frontier area between the British province of New York and the French province of Canada. The battle was given its name because the British combatants were wearing snowshoes.
Rogers led a band of about 180 rangers and regulars out to scout French positions. The French commander at Fort Carillon had been alerted to their movement, and sent a force consisting mostly of Indians to meet them. In fierce fighting, the British troop was nearly destroyed, with more than 120 casualties. The French believed that Rogers was killed in this action, as he was forced to abandon his regimental jacket, which contained his commission papers, during his escape from the scene.
This battle gave rise to the tale that Rogers escaped capture by sliding 400 feet (120 m) down a rockface to the frozen surface of Lake George. That rock is now known as Rogers Rock or Rogers Slide.
Contents
[hide]
1 Background
2 Prelude
3 Battle
4 Aftermath
5 See also
6 Notes
7 References
8 Further reading
9 External links
Background[edit]
Main articles: French and Indian War and Rogers' Rangers
The French and Indian War broke out in 1754 between British and French colonists over territorial disputes along their colonial frontiers, and escalated the following year to include regular troops.[4] By 1756, the French had enjoyed successes in most of their frontier battles against the British. Their only notable failure occurred when the British stopped their southward advance from Lake Champlain in the 1755 Battle of Lake George. From bases at Fort St. Frédéric (located at what is now Crown Point, New York) and Fort Carillon (known to the British as Fort Ticonderoga), the French and their Indian allies continued to scout and probe the British defenses on Lake George and the upper Hudson River.[5] The British, who had fewer Indian allies, resorted to companies of colonial rangers for their scouting and reconnaissance activities.[6] The ranger companies were organized and directed by Robert Rogers, and eventually became known as Rogers' Rangers.[7]
Prelude[edit]
Captain Rogers was sent on a reconnaissance mission from Fort Edward northwards toward Fort Carillon on March 10, 1758.[8] Lieutenant Colonel William Haviland, the fort's commander, had originally planned on 400 men taking part but reduced the number to 180,[9] even though he had reason to believe the French knew of the expedition. The French had captured a man from an earlier expedition by Israel Putnam's Connecticut rangers and it was suspected that he had informed his captors of the British plans. Putnam's reconnaissance revealed that there were an estimated 600 Indians encamped near Fort Carillon.[2]
The expedition was composed mostly of men from Rogers' ranger companies, but it also included a few volunteer soldiers from the 27th (Inniskilling) Regiment.[2] On March 13, they wore snowshoes as they marched through snow four feet deep, with a rivulet to their left and a steep mountain separating them from Lake George to their right. They had stopped for a three-hour break when their advance guard spotted what Rogers reported as "ninety-six, chiefly Indians".[10]
On March 12, Captain Louis-Philippe Le Dossu d’Hébécourt, the French commander at Fort Carillon, heard rumors from the encamped Indians that the British were nearing. He sent Ensign Durantaye with a company of 200 Nipissing Indians and about 20 Canadians in response to these reports, but they found nothing. The next day two Indian scouts reported that they had found tracks of an enemy party. Around noon on March 13, Durantaye led 100 men (again a mixed company of Indians and Canadians) out of the fort. These were followed shortly after by 200 Indians under Ensign de Langy.[1]
Although the two French groups joined forces, Durantaye's company was about 100 yards (91 m) ahead of Langy's when they were spotted by Rogers' men.[11]
Battle[edit]
Rogers’ men immediately set up an ambush. When Durantaye's men came within range at 14:00, the British opened fire, killing "above forty Indians", according to Rogers.[10] Durantaye's force broke and retreated in disarray. Rogers and about half his men gave chase, critically forgetting to reload their muskets, while the others stopped to collect scalps.[12] Langy's men, alerted by the gunfire, set up their own ambush. When Rogers' men arrived, the attack by Langy's force killed or wounded an estimated 50 men. The Rangers fought bravely, considering they were outnumbered and their numbers were falling quickly. They made several successful attempts to prevent themselves from being flanked, but after an hour and a half of heavy fighting, their numbers were significantly reduced. The remnants of the British force then tried to escape the battle. Rogers and some of his men did get away, but one group of men surrendered, only to be killed and scalped when a scalp was discovered in a pocket of one of the men.[13]
Aftermath[edit]
Rogers and his decimated company returned to Fort Edward on March 15.[14] Rogers himself was originally reported by the French to have been killed, but had actually survived. The report stemmed from the manner of Rogers’ escape during which he discarded some of his belongings, including his regimental coat, which contained his military commission.[15] This episode also gave rise to a local legend that Rogers escaped the battle by sliding 400 feet down the side of a hill to the frozen surface of Lake George. While there is no proof of this event, the rockface he supposedly went down very quickly became known as Rogers' Slide.[16]
Reports of casualties, and of the numbers of forces involved, starkly differed in this battle. Rogers' report of the event estimated the French-Indian force at 700, with one to two hundred casualties,[16] and his accounts of the battle were doubted by a variety of commentators, as they were inconsistent with other accounts. A letter by Henry Pringle, written while held in captivity at Carillon, restored his reputation by clarifying the French advantage following the second ambush; Rogers went on to rebuild his companies and serve in the Battle of Carillon in July 1758.[17]
See also[edit]
Battle of Carillon
List of conflicts in Canada
Notes[edit]
^ Jump up to: a b Nester (2008), p. 15
^ Jump up to: a b c Nester (2008), p. 10
^ Jump up to: a b Casualty figures are as reported by each side in Nester (2008), p. 17. Each side estimated the casualties on the other side to be somewhat higher. According to [1] French Casualties were totaled 30--8 Indians killed + 2 indians mortally wounded & 17 Indians and 3 Canadians wounded.
Jump up ^ Brumwell (2004), p. 55
Jump up ^ Brumwell (2004), pp. 59–82
Jump up ^ Brumwell (2004), pp. 70–71
Jump up ^ Brumwell (2004), pp. 103–105
Jump up ^ Nester (2008), p. 9
Jump up ^ Rogers (1883), p. 93
^ Jump up to: a b Rogers (1883), p. 96
Jump up ^ Nester (2008), p. 16
Jump up ^ Brumwell (2004), p. 114
Jump up ^ Brumwell (2004), p. 115
Jump up ^ Rogers (1883), p. 99
Jump up ^ Brumwell (2004), p. 117
^ Jump up to: a b Brumwell (2004), p. 118
Jump up ^ Brumwell (2004), p. 119–124
References[edit]
Brumwell, Stephen (2004). White Devil. Cambridge, MA: Da Capo. ISBN 0-306-81389-0. OCLC 57655778.
Nester, William (2008). The Epic Battles of the Ticonderoga, 1758. Albany, New York: State University of New York Press. ISBN 978-0-7914-7321-4. OCLC 105469157.
Rogers, Robert; Hough, Franklin Benjamin (1883). Journals of Major Robert Rogers. Albany, NY: Joel Munsell's Sons. OCLC 1999679.
Further reading[edit]
Bearor, Bob (1997). Battle On Snowshoes. Bowie, MD: Heritage Books. OCLC 37299292.
Bougainville, Louis Antoine de (1964). Hamilton, Edward P., ed. Adventures in the Wilderness. Norman, OK: University of Oklahoma Press. OCLC 506918.
Pajol, Charles Pierre Victor (1888). Les guerres sous Louis XV, Volume 6 (in French). Paris: Firmin-Didot. OCLC 3161767.
Parkman, Francis (1884). Montcalm and Wolfe. OCLC 178405593. . Multiple editions currently available.
Rogers, Mary Cochrane (1917). Rogers' Rock, Lake George, March 13, 1758: A Battle Fought on Snow Shoes. Derry, NH: self-publisher. OCLC 5039620.
Steele, Ian Kenneth (1990). Betrayals: Fort William Henry and the massacre. Oxford University Press US. ISBN 978-0-19-505893-2. OCLC 20098712.
Zaboly, Gary S (2004). A True Ranger: The Life and Many Wars of Major Robert Rogers. Garden City Park, NY: Royal Blockhouse. ISBN 978-0-9761701-0-5. OCLC 61311390.
External links[edit]
Rogers' Slide
New York State Military Museum article on the battle
Mohican Press fictional treatment of the battle
Documentary on the battle
Reenactment of the battle
The New York Independence Trail
Rogers Rock State Campground
Map showing the battle location and that of other French and Indian War battles
Pictures from the 2012 reenactment of the battle
Coordinates: 43°25′34″N 73°42′44″W / 43.42611°N 73.71222°W / 43.42611; -73.71222
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Property Brothers
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Property Brothers
Genre
Reality
Starring
Drew Scott
Jonathan Scott
Country of origin
Canada
Original language(s)
English
No. of seasons
10
No. of episodes
131 (as of March 15, 2017)
Production
Running time
45 minutes
Release
Original network
W Network
HGTV
Picture format
1080i (HDTV)
Original release
January 4, 2011 (2011-01-04) – present
External links
Website
www.wnetwork.com/Shows/PropertyBrothers.aspx
Property Brothers is a Canadian reality television series that is produced by Cineflix, and the original show in the Property Brothers franchise. It airs on W Network in Canada and HGTV in the United States. The series features identical twin brothers Jonathan and Drew Scott (born April 28, 1978) who help home buyers to purchase and renovate "fixer-uppers."[1] Drew is a real estate expert who scouts neglected houses and negotiates the purchases. His brother, Jonathan, is a licensed contractor who renovates houses. Together, the Property Brothers help families find, buy, and transform fixer-uppers into dream homes on a strict time-line and budget.[2][3]
Contents
[hide]
1 Development
2 Premise
3 Production
4 Presenters
5 Reception
6 Episodes
7 See also
8 Footnotes
8.1 References
8.2 Works cited
9 External links
Development[edit]
In 1996,[4] Jonathan and Drew Scott first began working in the real estate and design fields to financially support themselves as actors.[5] However, after ten years went by with little to no acting jobs, Drew decided to return to acting full-time.[6] He was offered a gig as a host of a real estate competition show that ultimately didn't materialize.[7] But, when it was discovered that he had a twin brother who was also in the real estate business, Cineflix pitched the idea of a reality show with each of them in different roles.[5][7] They filmed a pilot for the show in 2009.[8] Originally, the network wanted Drew to work as the contractor because of his physique; when they realized that Jonathan was licensed, they switched the roles.[9]
About six months went by with no offers, when (off the strength of the pilot) the W Network in Canada ordered a full season;[8] meanwhile HGTV passed.[8] Aware of the show's success in Canada, HGTV condensed the existing episodes to 30 minutes and aired them on a trial basis.[8] After the show scored number-one ratings for its timeslot, the network picked the show up for distribution in the US.[8]
Premise[edit]
Using the expertise of twin brothers Drew and Jonathan Scott, prospective homebuyers find a "fixer-upper" and remodel it into their dream home while staying within their budget. The featured families and individuals are often working towards a deadline, like the birth of a child or a special occasion. Historically, each episode started with Drew showing potential homebuyers a house with everything on their wish list, only to later reveal that the house was outside of their reach financially. However, beginning with season 10, Drew began to explain from the start that the home would exceed their budget. In either scenario, he and Jonathan then highlight the advantages of purchasing an older home. After Drew then takes the buyers on a tour of homes that are significantly less ideal, but have renovation potential, they are asked to narrow their choices down to two. The brothers then use computer-generated imagery to reveal their re-imagined vision of the home after significant renovations. The graphics are made by an outside company using Neezo Renders software at a cost about $10,000 per episode.[10][11] After the family makes a final decision, Drew leads them through the process of bidding on and purchasing a home. Once a purchase is made, Jonathan and his team begin renovations. The family is kept away after initial demolition, and are brought back at the conclusion for the final reveal.
Production[edit]
The show's producers choose cities for filming based a variety of factors including fan interest, proximity to a major airport, and local building ordinances.[citation needed] Typical of home improvement shows with an accelerated renovation format, three experienced crews work on the house in tandem to finish in the four to seven week timeline.[citation needed] The brothers hire local design, real estate, and construction companies in the cities where they film,[12] Additionally building permits are typically ready prior to construction,[citation needed] and their projects take priority with the suppliers.[13][11] The buyers own the property and pay for the remodeling, but the show is able to provide about $20,000 to $25,000 worth of cash and furnishings.[14][11] The brothers do not charge for their services.[11] The total budget presented is for the three or four rooms featured on the show; the rest of the renovations are done off-camera on a separate budget and timeline.[11]
Persons interested in appearing on the show must come with a shortlist of homes or a home they plan to buy, though Drew provides additional options, and reserves the right to reject their selection if the home is unsafe.[15] Applicants must apply as a couple (whether they be spouses, partners, friends, or family), and have financing ready with a budget of at least $65,000 USD with a 25-percent contingency for unexpected expenses.[11][16] Producers screen applicants for their ability to make quick decisions and the ability to film for at least eight weekdays during the project.[16]
The brothers have maintained that their shows are not contrived or scripted.[17] Homeowners are not provided with storylines or dialog and unforeseen construction challenges are real.[18] Additionally, the homebuyers work with real project budgets,[2] However, the brothers concede that conversations may be re-shot and incidents may be reconstructed due to disruptions on set (eg. a plane flying overhead), to highlight how protracted problems were resolved, or because the cameras did not capture the real-time shot.[19][20]
The first season was recorded in Toronto, Ontario, Canada.[21] For the third season, the show was recorded in Austin, Texas, for half of the year and Toronto for the rest.[14] Part of the reason for the move was the fact that American audiences couldn't relate to the higher market prices in Canada.[11] The brothers returned to their hometown of Vancouver, British Columbia to film in 2013.[13] In 2014, the show recorded several episodes in Atlanta, Georgia and Toronto. Between 2015 and 2016 they filmed in Westchester County, New York.[22][23] In 2017, they will be filming in Nashville, Tennessee.
Presenters[edit]
Main articles: Jonathan Scott (Canadian actor) and Drew Scott
Drew (left) and Jonathan Scott at the 2015 World Dog Awards
Before going into real estate as a profession, the brothers tried acting, including minor roles in Breaker High, Smallville, and X-Files.[24] Drew aspired to be an actor, while Jonathan sought a career as an illusionist.[citation needed] In the meantime, they bought their first house when they were 18 years old university students and, after renovations, sold it a year later for a $50,000 profit.[25] In 2004, they founded Scott Real Estate, Inc., a company that oversees the sales and construction of residential and commercial projects, with offices in Vancouver, Calgary, and Las Vegas.[3] Their business soon grew and they were approached to do the television show.[24] At the show's start, the twins had managed real estate holdings for nearly 15 years.[5][26][24]
Both brothers are licensed real estate agents.[citation needed] Drew was licensed in early 2004 and continues to be a licensed agent with Keller Williams Elite in British Columbia.[citation needed] Jonathan became a licensed agent in Las Vegas after opening an office there in 2008.[citation needed] Jonathan is also a licensed contractor.[citation needed]
The show is broadcast in over 150 countries, and is dubbed in many languages.[citation needed] The voices of both brothers is provided by the same voice actor in Spanish.[24]
Reception[edit]
The show has consistently been the highest rated on HGTV during its run, and as of 2017 Property Brothers remains HGTV's highest rated show.[27]. It is broadcast in 150 countries and territories.[20] The fifth season attracted more than 10 million viewers between 24 – 54 age demographic, and consistently ranked as a top five cable program among upscale women in the 25 – 54 age group.[28] In 2016, the show averaged 1.3 million viewers weekly.[29]
Consumer Reports put it on its list of best home improvement shows, saying, "We all wish Drew and Jonathan were our big brothers—and that they’d help us find our dream home."[30]
Property Brothers has won multiple awards. After being nominated in 2011, Drew and Jonathan won the 2012 Leo Award (the awards program for the British Columbia film and television industry) for "Best Host(s) in an Information or Lifestyle Series" for Property Brothers.[31] In 2012, they were nominated for a Rose d'Or award in the lifestyle show category.[11][32] The show's been nominated for a Cablefax Award and for Outstanding Structured Reality Program at the 2015 Emmy Awards.[33][34]
The program has had an impact on popular culture, and has been the subject of multiple jokes on Brooklyn 99,[35][36] as well as Unbreakable Kimmy Schmidt.[37][38]
Episodes[edit]
Main article: List of Property Brothers episodes
Season
HGTV Season
Episodes
Filming Location
First aired
Last aired
1 1 13 Toronto January 4, 2011 (2011-01-04) March 29, 2011 (2011-03-29)
2 2 13 Toronto October 20, 2011 (2011-10-20) January 31, 2012 (2012-01-31)
4 13 Austin February 7, 2012 (2012-02-07) May 1, 2012 (2012-05-01)
3 3 13 Austin/Toronto January 9, 2013 (2013-01-09) April 3, 2013 (2013-04-03)
5 13 Vancouver August 28, 2013 (2013-08-28) November 20, 2013 (2013-11-20)
4 6 13 Atlanta March 12, 2014 (2014-03-12) August 27, 2014 (2014-08-27)
7 13 Toronto January 7, 2015 (2015-01-07) May 17, 2015 (2015-05-17)
5 8 14 Westchester County October 7, 2015 (2015-10-07) February 10, 2016 (2016-02-10)
9 13 Westchester County February 17, 2016 (2016-02-17) November 2, 2016 (2016-11-02)
6 10 N/A Westchester County November 16, 2016 (2016-11-16) 2017 (2017)
See also[edit]
Love It or List It
Income Property
Divine Design
Fixer Upper
Footnotes[edit]
References[edit]
Jump up ^ Wilson, Jennifer (14 October 2011). "'We have the same creative spirit'; Drew and Jonathan Scott — twin brothers — are the perfect designing duo". Toronto Star. Retrieved 17 January 2012.
^ Jump up to: a b "Interview: Property Brothers Jonathan and Drew Scott Fix Up Canada". Real Style. 25 January 2011. Retrieved 17 January 2012.
^ Jump up to: a b HGTV. "Drew Scott and Jonathan Scott". Retrieved 15 April 2012.
Jump up ^ HURT, MELONEE MCKINNEY (May 2012),"Bet on the House". Men's Health. 27 (4):66
^ Jump up to: a b c Glionna, John (March 8, 2015). "Twins Flip Homes and Expectations". Los Angeles Times.
Jump up ^ Kurutz, Steven (August 21, 2014), "Hey, Here's an Idea for a Show". New York Times. 163 (56600):D1-D7
^ Jump up to: a b Berk, Nancy (August 14, 2015), "Property Brother Jonathan Scott Discusses the Power of 15-Minute Renovations". Parade. Retrieved February 6, 2017.
^ Jump up to: a b c d e Scott & Scott 2016, p. 21.
Jump up ^ Scott & Scott 2017, p. 218.
Jump up ^ Real Style staff (September 2012), "Interview: Property Brothers Drew & Jonathan Scott On Women, Dating & The New Season". Real Style. Retrieved January 30, 2017.
^ Jump up to: a b c d e f g h Hussain, Tania (March 13, 2012), "The Two Skillful Brothers Scott: TV's 'Property Brothers' Finding and Building Dream Homes". West Life Bunny. Retrieved March 8, 2017.
Jump up ^ Stevens, Kimberly (September 6, 2014), "For Home-Improvement Show Hosts, a Paradox: Every House but Their Own". LA Times. Retrieved March 10, 2017.
^ Jump up to: a b Gold, Kerry (March 18, 2013), "The Property Brothers are back home – and on the hunt for bargains". The Globe and Mail. Retrieved March 8, 2017.
^ Jump up to: a b Nicole Villalpando, "Property Brothers transforming Austin homes for TV", Austin American-Statesman, February 25, 2012, accessed May 1, 2013.
Jump up ^ Scott & Scott 2017, p. 226 – 227.
^ Jump up to: a b Winterfeldt, Maggie (2015-11-30). "The Truth About Getting Your Home Renovated on Property Brothers". MSN. Retrieved 25 September 2017.
Jump up ^ Scott & Scott 2017, p. 214.
Jump up ^ Scott & Scott 2017, p. 215.
Jump up ^ Scott & Scott 2017, pp. 214 – 215.
^ Jump up to: a b Rosman, Katherine (May 10, 2017), "The Property Brothers Are Fixing to Take Over the World". The New York Times. Retrieved May 10, 2017.
Jump up ^ Adair, Connie. "Property Brothers the Latest Real Estate TV Stars". Retrieved 6 February 2013.
Jump up ^ "HGTV's Property Brothers Finish Run in Atlanta" (29 April 2014) RadioTV Talk
Jump up ^ Propety Brothers Filming in Westchester" (3 March 2015) Lohud
^ Jump up to: a b c d Lauren Brown (20 June 2012), "10 Amazing Secrets About HGTV's Property Brothers Jonathan and Drew Scott—AKA Your New Crushes". Glamour. Retrieved May 1, 2013.
Jump up ^ Cockrell, Katie (7 February 2011). "Meet the Property Brothers". Archived from the original on 14 March 2011. Retrieved 15 April 2012.
Jump up ^ Lifestyle staff, "Jonathan Scott and Drew Scott". Lifestyle.com. Retrieved February 8, 2017.
Jump up ^ Tablang, Kristin (January 26, 2017), "Online Exclusive: 'Property Brothers' Jonathan and Drew Scott Launch Dream Homes by Scott Living." . Forbes. Retrieved February 12, 2017.
Jump up ^ "HGTV's Property Brothers return with 2nd seasons of Buying and Selling and Brother vs. Brother" (Press release). Scripps Networks Interactive. November 21, 2013. Retrieved March 4, 2017.
Jump up ^ Blas, Lorena (November 21, 2016), "The twin 'Property Brothers' are stars of HGTV". USA TODAY. Retrieved March 3, 2017.
Jump up ^ Consumer Reports staff (March 2015), "The Best & Worst Home Shows on TV". Consumer Reports. 80 (3):31
Jump up ^ "Drew Scott Awards". IMDB.
Jump up ^ "3 Canadians up for Rose D'or Award". CBC Canada. February 2012. Retrieved September 22, 2017.
Jump up ^ "Program Awards". Cablefax. Retrieved January 30, 2017.
Jump up ^ "Property Brothers Awards & Nominations". Emmys. Retrieved January 30, 2015.
Jump up ^ Pape, Allie (April 6, 2016). "Brooklyn Nine-Nine Recap: Let’s Go to Prison". Vulture. Retrieved 24 May 2017.
Jump up ^ @MrDrewScott (21 May 2017). "Another reason I love @Brooklyn99FOX! 😂 #PropertyBrothers @JoeLoTruglio @iamstephbeatz @terrycrews @thelonelyisland" (Tweet) – via Twitter.
Jump up ^ "Kimmy Kidnaps Gretchen!". Unbreakable Kimmy Schmidt. Season 2. Episode 4. April 15, 2016. Netflix. Retrieved May 24, 2017. Titus, I'm the one who'd have to Property Brothers this gut job.
Jump up ^ Scott, Jonathan (May 21, 2017). "You pegged Drew at least 😂 @unbreakablekimmyschmidt #JaneKrakowski". Instagram. Retrieved 24 May 2017.
Works cited[edit]
Scott, Drew; Scott, Jonathan (April 2016). Dream Home: The Property Brothers’ Ultimate Guide to Finding & Fixing Your Perfect House. New York: Houghton Mifflin Harcourt. ISBN 0-544715-67-5.
Scott, Jonathan; Scott, Drew (September 5, 2017). It Takes Two: Our Story. Houghton Mifflin Harcourt. p. 304. ISBN 1328771474.
External links[edit]
The Scott Brothers site
W Network site
HGTV site
Property Brothers on IMDb
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Messenger RNA
From Wikipedia, the free encyclopedia
Jump to: navigation, search
The "life cycle" of an mRNA in a eukaryotic cell. RNA is transcribed in the nucleus; processing, it is transported to the cytoplasm and translated by the ribosome. Finally, the mRNA is degraded.
Messenger RNA (mRNA) is a large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression. Following transcription of primary transcript mRNA (known as pre-mRNA) by RNA polymerase, processed, mature mRNA is translated into a polymer of amino acids: a protein, as summarized in the central dogma of molecular biology.
As in DNA, mRNA genetic information is in the sequence of nucleotides, which are arranged into codons consisting of three base pairs each. Each codon encodes for a specific amino acid, except the stop codons, which terminate protein synthesis. This process of translation of codons into amino acids requires two other types of RNA: Transfer RNA (tRNA), that mediates recognition of the codon and provides the corresponding amino acid, and ribosomal RNA (rRNA), that is the central component of the ribosome's protein-manufacturing machinery.
The existence of mRNA was first suggested by Jacques Monod and François Jacob, and subsequently discovered by Jacob, Sydney Brenner and Matthew Meselson at the California Institute of Technology in 1961.
It should not be confused with mitochondrial DNA.
Contents
[hide]
1 Synthesis, processing and function
1.1 Transcription
1.2 Eukaryotic pre-mRNA processing
1.2.1 5' cap addition
1.2.2 Editing
1.2.3 Polyadenylation
1.3 Transport
1.4 Translation
2 Structure
2.1 Coding regions
2.2 Untranslated regions
2.3 Poly(A) tail
2.4 Monocistronic versus polycistronic mRNA
2.5 mRNA circularization
3 Degradation
3.1 Prokaryotic mRNA degradation
3.2 Eukaryotic mRNA turnover
3.3 AU-rich element decay
3.4 Nonsense mediated decay
3.5 Small interfering RNA (siRNA)
3.6 MicroRNA (miRNA)
3.7 Other decay mechanisms
4 mRNA-based therapeutics
5 See also
6 References
7 External links
Synthesis, processing and function[edit]
The brief existence of an mRNA molecule begins with transcription, and ultimately ends in degradation. During its life, an mRNA molecule may also be processed, edited, and transported prior to translation. Eukaryotic mRNA molecules often require extensive processing and transport, while prokaryotic mRNA molecules do not. A molecule of eukaryotic mRNA and the proteins surrounding it are together called a messenger RNP.
Transcription[edit]
Main article: Transcription (genetics)
Transcription is when RNA is made from DNA. During transcription, RNA polymerase makes a copy of a gene from the DNA to mRNA as needed. This process is similar in eukaryotes and prokaryotes. One notable difference, however, is that eukaryotic RNA polymerase associates with mRNA-processing enzymes during transcription so that processing can proceed quickly after the start of transcription. The short-lived, unprocessed or partially processed product is termed precursor mRNA, or pre-mRNA; once completely processed, it is termed mature mRNA.
Eukaryotic pre-mRNA processing[edit]
Main article: Post-transcriptional modification
Processing of mRNA differs greatly among eukaryotes, bacteria, and archea. Non-eukaryotic mRNA is, in essence, mature upon transcription and requires no processing, except in rare cases. Eukaryotic pre-mRNA, however, requires extensive processing.
5' cap addition[edit]
Main article: 5' cap
A 5' cap (also termed an RNA cap, an RNA 7-methylguanosine cap, or an RNA m7G cap) is a modified guanine nucleotide that has been added to the "front" or 5' end of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of a terminal 7-methylguanosine residue that is linked through a 5'-5'-triphosphate bond to the first transcribed nucleotide. Its presence is critical for recognition by the ribosome and protection from RNases.
Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is bound by a cap-synthesizing complex associated with RNA polymerase. This enzymatic complex catalyzes the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step biochemical reaction.
Editing[edit]
In some instances, an mRNA will be edited, changing the nucleotide composition of that mRNA. An example in humans is the apolipoprotein B mRNA, which is edited in some tissues, but not others. The editing creates an early stop codon, which, upon translation, produces a shorter protein.
Polyadenylation[edit]
Main article: Polyadenylation
Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. In eukaryotic organisms most messenger RNA (mRNA) molecules are polyadenylated at the 3' end, but recent studies have shown that short stretches of uridine (oligouridylation) are also common.[1] The poly(A) tail and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. mRNA can also be polyadenylated in prokaryotic organisms, where poly(A) tails act to facilitate, rather than impede, exonucleolytic degradation.
Polyadenylation occurs during and/or immediately after transcription of DNA into RNA. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. After the mRNA has been cleaved, around 250 adenosine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by polyadenylate polymerase. Just as in alternative splicing, there can be more than one polyadenylation variant of an mRNA.
Polyadenylation site mutations also occur. The primary RNA transcript of a gene is cleaved at the poly-A addition site, and 100-200 A’s are added to the 3’ end of the RNA. If this site is altered, an abnormally long and unstable mRNA construct will be formed.
Transport[edit]
Another difference between eukaryotes and prokaryotes is mRNA transport. Because eukaryotic transcription and translation is compartmentally separated, eukaryotic mRNAs must be exported from the nucleus to the cytoplasm—a process that may be regulated by different signaling pathways.[2] Mature mRNAs are recognized by their processed modifications and then exported through the nuclear pore by binding to the cap-binding proteins CBP20 and CBP80,[3] as well as the transcription/export complex (TREX).[4][5] Multiple mRNA export pathways have been identified in eukaryotes.[6]
In spatially complex cells, some mRNAs are transported to particular subcellar destinations. In mature neurons, certain mRNA are transported from the soma to dendrites. One site of mRNA translation is at polyribosomes selectively localized beneath synapses.[7] The mRNA for Arc/Arg3.1 is induced by synaptic activity and localizes selectively near active synapses based on signals generated by NMDA receptors.[8] Other mRNAs also move into dendrites in response to external stimuli, such as β-actin mRNA.[9] Upon export from the nucleus, actin mRNA associates with ZBP1 and the 40S subunit. The complex is bound by a motor protein and is transported to the target location (neurite extension) along the cytoskeleton. Eventually ZBP1 is phosphorylated by Src in order for translation to be initiated.[10] In developing neurons, mRNAs are also transported into growing axons and especially growth cones. Many mRNAs are marked with so-called "zip codes," which target their transport to a specific location.[11]
Translation[edit]
Main article: Translation (genetics)
Because prokaryotic mRNA does not need to be processed or transported, translation by the ribosome can begin immediately after the end of transcription. Therefore, it can be said that prokaryotic translation is coupled to transcription and occurs co-transcriptionally.
Eukaryotic mRNA that has been processed and transported to the cytoplasm (i.e., mature mRNA) can then be translated by the ribosome. Translation may occur at ribosomes free-floating in the cytoplasm, or directed to the endoplasmic reticulum by the signal recognition particle. Therefore, unlike in prokaryotes, eukaryotic translation is not directly coupled to transcription.[12]
Structure[edit]
The structure of a mature eukaryotic mRNA. A fully processed mRNA includes a 5' cap, 5' UTR, coding region, 3' UTR, and poly(A) tail.
Coding regions[edit]
Main article: Coding region
Coding regions are composed of codons, which are decoded and translated (in eukaryotes usually into one and in prokaryotes usually into several) into proteins by the ribosome. Coding regions begin with the start codon and end with a stop codon. In general, the start codon is an AUG triplet and the stop codon is UAA, UAG, or UGA. The coding regions tend to be stabilised by internal base pairs, this impedes degradation.[13][14] In addition to being protein-coding, portions of coding regions may serve as regulatory sequences in the pre-mRNA as exonic splicing enhancers or exonic splicing silencers.
Untranslated regions[edit]
Main articles: 5' UTR and 3' UTR
Untranslated regions (UTRs) are sections of the mRNA before the start codon and after the stop codon that are not translated, termed the five prime untranslated region (5' UTR) and three prime untranslated region (3' UTR), respectively. These regions are transcribed with the coding region and thus are exonic as they are present in the mature mRNA. Several roles in gene expression have been attributed to the untranslated regions, including mRNA stability, mRNA localization, and translational efficiency. The ability of a UTR to perform these functions depends on the sequence of the UTR and can differ between mRNAs. Genetic variants in 3' UTR have also been implicated in disease susceptibility because of the change in RNA structure and protein translation.[15]
The stability of mRNAs may be controlled by the 5' UTR and/or 3' UTR due to varying affinity for RNA degrading enzymes called ribonucleases and for ancillary proteins that can promote or inhibit RNA degradation. (See also, C-rich stability element.)
Translational efficiency, including sometimes the complete inhibition of translation, can be controlled by UTRs. Proteins that bind to either the 3' or 5' UTR may affect translation by influencing the ribosome's ability to bind to the mRNA. MicroRNAs bound to the 3' UTR also may affect translational efficiency or mRNA stability.
Cytoplasmic localization of mRNA is thought to be a function of the 3' UTR. Proteins that are needed in a particular region of the cell can also be translated there; in such a case, the 3' UTR may contain sequences that allow the transcript to be localized to this region for translation.
Some of the elements contained in untranslated regions form a characteristic secondary structure when transcribed into RNA. These structural mRNA elements are involved in regulating the mRNA. Some, such as the SECIS element, are targets for proteins to bind. One class of mRNA element, the riboswitches, directly bind small molecules, changing their fold to modify levels of transcription or translation. In these cases, the mRNA regulates itself.
Poly(A) tail[edit]
Main article: Polyadenylation
The 3' poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the 3' end of the pre-mRNA. This tail promotes export from the nucleus and translation, and protects the mRNA from degradation.
Monocistronic versus polycistronic mRNA[edit]
See also: Cistron
An mRNA molecule is said to be monocistronic when it contains the genetic information to translate only a single protein chain (polypeptide). This is the case for most of the eukaryotic mRNAs.[16][17] On the other hand, polycistronic mRNA carries several open reading frames (ORFs), each of which is translated into a polypeptide. These polypeptides usually have a related function (they often are the subunits composing a final complex protein) and their coding sequence is grouped and regulated together in a regulatory region, containing a promoter and an operator. Most of the mRNA found in bacteria and archaea is polycistronic,[16] as is the human mitochondrial genome[18] . Dicistronic or bicistronic mRNA encodes only two proteins.
mRNA circularization[edit]
In eukaryotes mRNA molecules form circular structures due to an interaction between the eIF4E and poly(A)-binding protein, which both bind to eIF4G, forming an mRNA-protein-mRNA bridge.[19] Circularization is thought to promote cycling of ribosomes on the mRNA leading to time-efficient translation, and may also function to ensure only intact mRNA are translated (partially degraded mRNA characteristically have no m7G cap, or no poly-A tail).[20]
Other mechanisms for circularization exist, particularly in virus mRNA. Poliovirus mRNA uses a cloverleaf section towards its 5' end to bind PCBP2, which binds poly(A)-binding protein, forming the familiar mRNA-protein-mRNA circle. Barley yellow dwarf virus has binding between mRNA segments on its 5' end and 3' end (called kissing stem loops), circularizing the mRNA without any proteins involved.
RNA virus genomes (the + strands of which are translated as mRNA) are also commonly circularized.[citation needed] During genome replication the circularization acts to enhance genome replication speeds, cycling viral RNA-dependent RNA polymerase much the same as the ribosome is hypothesized to cycle.
Degradation[edit]
Different mRNAs within the same cell have distinct lifetimes (stabilities). In bacterial cells, individual mRNAs can survive from seconds to more than an hour; in mammalian cells, mRNA lifetimes range from several minutes to days.[21] The greater the stability of an mRNA the more protein may be produced from that mRNA. The limited lifetime of mRNA enables a cell to alter protein synthesis rapidly in response to its changing needs. There are many mechanisms that lead to the destruction of an mRNA, some of which are described below.
Prokaryotic mRNA degradation[edit]
In general, in prokaryotes the lifetime of mRNA is much shorter than in eukaryotes. Prokaryotes degrade messages by using a combination of ribonucleases, including endonucleases, 3' exonucleases, and 5' exonucleases. In some instances, small RNA molecules (sRNA) tens to hundreds of nucleotides long can stimulate the degradation of specific mRNAs by base-pairing with complementary sequences and facilitating ribonuclease cleavage by RNase III. It was recently shown that bacteria also have a sort of 5' cap consisting of a triphosphate on the 5' end.[22] Removal of two of the phosphates leaves a 5' monophosphate, causing the message to be destroyed by the exonuclease RNase J, which degrades 5' to 3'.
Eukaryotic mRNA turnover[edit]
Inside eukaryotic cells, there is a balance between the processes of translation and mRNA decay. Messages that are being actively translated are bound by ribosomes, the eukaryotic initiation factors eIF-4E and eIF-4G, and poly(A)-binding protein. eIF-4E and eIF-4G block the decapping enzyme (DCP2), and poly(A)-binding protein blocks the exosome complex, protecting the ends of the message. The balance between translation and decay is reflected in the size and abundance of cytoplasmic structures known as P-bodies[23] The poly(A) tail of the mRNA is shortened by specialized exonucleases that are targeted to specific messenger RNAs by a combination of cis-regulatory sequences on the RNA and trans-acting RNA-binding proteins. Poly(A) tail removal is thought to disrupt the circular structure of the message and destabilize the cap binding complex. The message is then subject to degradation by either the exosome complex or the decapping complex. In this way, translationally inactive messages can be destroyed quickly, while active messages remain intact. The mechanism by which translation stops and the message is handed-off to decay complexes is not understood in detail.
AU-rich element decay[edit]
The presence of AU-rich elements in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these sequences and stimulate poly(A) tail removal. Loss of the poly(A) tail is thought to promote mRNA degradation by facilitating attack by both the exosome complex[24] and the decapping complex.[25] Rapid mRNA degradation via AU-rich elements is a critical mechanism for preventing the overproduction of potent cytokines such as tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF).[26] AU-rich elements also regulate the biosynthesis of proto-oncogenic transcription factors like c-Jun and c-Fos.[27]
Nonsense mediated decay[edit]
Main article: Nonsense mediated decay
Eukaryotic messages are subject to surveillance by nonsense mediated decay (NMD), which checks for the presence of premature stop codons (nonsense codons) in the message. These can arise via incomplete splicing, V(D)J recombination in the adaptive immune system, mutations in DNA, transcription errors, leaky scanning by the ribosome causing a frame shift, and other causes. Detection of a premature stop codon triggers mRNA degradation by 5' decapping, 3' poly(A) tail removal, or endonucleolytic cleavage.[28]
Small interfering RNA (siRNA)[edit]
Main article: siRNA
In metazoans, small interfering RNAs (siRNAs) processed by Dicer are incorporated into a complex known as the RNA-induced silencing complex or RISC. This complex contains an endonuclease that cleaves perfectly complementary messages to which the siRNA binds. The resulting mRNA fragments are then destroyed by exonucleases. siRNA is commonly used in laboratories to block the function of genes in cell culture. It is thought to be part of the innate immune system as a defense against double-stranded RNA viruses.[29]
MicroRNA (miRNA)[edit]
Main article: microRNA
MicroRNAs (miRNAs) are small RNAs that typically are partially complementary to sequences in metazoan messenger RNAs.[30] Binding of a miRNA to a message can repress translation of that message and accelerate poly(A) tail removal, thereby hastening mRNA degradation. The mechanism of action of miRNAs is the subject of active research.[31]
Other decay mechanisms[edit]
There are other ways by which messages can be degraded, including non-stop decay and silencing by Piwi-interacting RNA (piRNA), among others.
mRNA-based therapeutics[edit]
Full length mRNA molecules have been proposed as therapeutics since the beginning of the biotech era but there was little traction until the 2010s, when Moderna Therapeutics was founded and managed to raise almost a billion dollars in venture funding in its first three years.[32][33][34][35]
Theoretically, the administered mRNA sequence can cause a cell to make a protein, which in turn could directly treat a disease or could function as a vaccine; more indirectly the protein could drive an endogenous stem cell to differentiate in a desired way.[36][37]
The primary challenges of RNA therapy center on delivering the RNA to directed cells, more even than determining what sequence to deliver.[33] Naked RNA sequences will naturally degrade after preparation; they may trigger the body's immune system to attack them as an invader; and they are impermeable to the cell membrane[37]. Once within the cell, they must then leave the cell's transport mechanism to take action within the cytoplasm, which houses the ribosomes that direct manufacture of proteins.[36]
See also[edit]
Transcriptome, the sum of all RNA in a cell
GeneCalling, an mRNA profiling technology
References[edit]
Jump up ^ Choi et al. RNA. 2012. 18: 394-401
Jump up ^ Quaresma, Alexandre J.; Sievert, Jeffrey A.; Nickerson, J. A. (2013), "Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway", Mol Biol Cell, 24 (8): 1208–21, PMC 3623641  , PMID 23427269, doi:10.1091/mbc.E12-06-0450
Jump up ^ Kierzkowski, Daniel; Kmieciak, Maciej; Piontek, Paulina; Wojtaszek, Przemyslaw; Szweykowska-Kulinska, Zofia; Jarmolowski, Artur (September 2009). "The Arabidopsis CBP20 targets the cap-binding complex to the nucleus, and is stabilized by CBP80". The Plant Journal. 59 (5): 814–825. doi:10.1111/j.1365-313X.2009.03915.x. Retrieved 12 December 2014.
Jump up ^ Sträßer, Katja; Masuda, Seiji; Mason, Paul; Pfannstiel, Jens; Oppizzi, Marisa; Rodriguez-Navarro, Susana; Rondón, Ana G.; Aguilera, Andres; Struhl, Kevin; Reed, Robin; Hurt, Ed (28 April 2002). "TREX is a conserved complex coupling transcription with messenger RNA export". Nature. 417 (6886): 304–308. PMID 11979277. doi:10.1038/nature746. Retrieved 12 December 2014.
Jump up ^ Katahira, Jun; Yoneda, Yoshihiro (27 October 2014). "Roles of the TREX complex in nuclear export of mRNA". RNA Biology. 6 (2): 149–152. doi:10.4161/rna.6.2.8046. Retrieved 12 December 2014.
Jump up ^ Cenik, Can; Chua, Hon Nian; Zhang, Hui; Tarnawsky, Stefan P.; Akef, Abdalla; Derti, Adnan; Tasan, Murat; Moore, Melissa J.; Palazzo, Alexander F.; Roth, Frederick P. (2011). "Genome Analysis Reveals Interplay between 5′UTR Introns and Nuclear mRNA Export for Secretory and Mitochondrial Genes". PLoS Genetics. 7 (4): e1001366. ISSN 1553-7404. PMC 3077370  . PMID 21533221. doi:10.1371/journal.pgen.1001366.
Jump up ^ Steward, Oswald. "Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus". Journal of Neuroscience. 2: 284–291.
Jump up ^ Steward, Oswald (2001). "Selective targeting of newly-synthesized Arc mRNA to active synapses requires NMDA receptor activation.". Neuron. 30: 227–240. PMID 11343657. doi:10.1016/s0896-6273(01)00275-6.
Jump up ^ Job, C.; Eberwine, J. (1912), "Localization and translation of mRNA in dendrites and axons", Nat Rev Neurosci, 2 (12): 889–98, PMID 11733796, doi:10.1038/35104069
Jump up ^ Spatial regulation of bold beta-actin translation by Src-dependent phosphorylation of ZBP1 Nature04115.
Jump up ^ Ainger, Kevin; Avossa, Daniela; Diana, Amy S.; Barry, Christopher; Barbarese, Elisa; Carson, John H. (1997), "Transport and Localization Elements in Myelin Basic Protein mRNA", The Journal of Cell Biology, 138 (5): 1077–1087, PMC 2136761  , PMID 9281585, doi:10.1083/jcb.138.5.1077
Jump up ^ somalia
Jump up ^ Shabalina SA, Ogurtsov AY, Spiridonov NA (2006), "A periodic pattern of mRNA secondary structure created by the genetic code", Nucleic Acids Res., 34 (8): 2428–37, PMC 1458515  , PMID 16682450, doi:10.1093/nar/gkl287
Jump up ^ Katz L, Burge CB (September 2003), "Widespread Selection for Local RNA Secondary Structure in Coding Regions of Bacterial Genes", Genome Res., 13 (9): 2042–51, PMC 403678  , PMID 12952875, doi:10.1101/gr.1257503
Jump up ^ Lu, YF; Mauger, DM; Goldstein, DB; Urban, TJ; Weeks, KM; Bradrick, SS (4 November 2015). "IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance.". Scientific Reports. 5: 16037. PMC 4631997  . PMID 26531896. doi:10.1038/srep16037.
^ Jump up to: a b Kozak, M. (March 1983), "Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles", Microbiological Reviews, 47 (1): 1–45, PMC 281560  , PMID 6343825
Jump up ^ Niehrs C, Pollet N (December 1999), "Synexpression groups in eukaryotes", Nature, 402 (6761): 483–7, PMID 10591207, doi:10.1038/990025
Jump up ^ Mercer, Tim R.; Neph, Shane; Dinger, Marcel E.; Crawford, Joanna; Smith, Martin A.; Shearwood, Anne-Marie J.; Haugen, Eric; Bracken, Cameron P.; Rackham, Oliver; Stamatoyannopoulos, John A.; Filipovska, Aleksandra; Mattick, John S. (2011). "The Human Mitochondrial Transcriptome". Cell. 146 (4): 645–658. ISSN 0092-8674. PMC 3160626  . doi:10.1016/j.cell.2011.06.051.
Jump up ^ Wells, S.E.; Hillner, P.E.; Vale, R.D.; Sachs, A.B. (1998), "Circularization of mRNA by Eukaryotic Translation Initiation Factors" (w), Molecular Cell, 2 (1): 135–140, PMID 9702200, doi:10.1016/S1097-2765(00)80122-7
Jump up ^ López-Lastra M, Rivas A, Barría MI (2005), "Protein synthesis in eukaryotes: The growing biological relevance of cap-independent translation initiation", Biological Research, 38: 121–146, PMID 16238092, doi:10.4067/S0716-97602005000200003 CS1 maint: Uses authors parameter (link)
Jump up ^ Yu, Jia; Russell, J. Eric. "Structural and Functional Analysis of an mRNP Complex That Mediates the High Stability of Human β-Globin mRNA" (PDF). Mol Cell Biol. 21: 5879–88. PMC 87307  . PMID 11486027. doi:10.1128/mcb.21.17.5879-5888.2001. Retrieved 4 June 2014.
Jump up ^ Deana, Atilio; Celesnik, Helena; Belasco, Joel G. (2008), "The bacterial enzyme RppH triggers messenger RNA degradation by 5' pyrophosphate removal", Nature, 451 (7176): 355–8, PMID 18202662, doi:10.1038/nature06475
Jump up ^ Parker, R.; Sheth, U. (2007), "P Bodies and the Control of mRNA Translation and Degradation" (w), Molecular Cell, 25 (5): 635–646, PMID 17349952, doi:10.1016/j.molcel.2007.02.011
Jump up ^ Chen, C.Y.; Gherzi, R.; Ong, S.E.; Chan, E.L.; Raijmakers, R.; Pruijn, G.J.M.; Stoecklin, G.; Moroni, C.; Mann, M.; Karin, Michael (2001), "AU Binding Proteins Recruit the Exosome to Degrade ARE-Containing mRNAs", Cell, 107 (4): 451–464, PMID 11719186, doi:10.1016/S0092-8674(01)00578-5
Jump up ^ Fenger-Grøn M, Fillman C, Norrild B, Lykke-Andersen J (December 2005), "Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping" (PDF), Mol. Cell, 20 (6): 905–15, PMID 16364915, doi:10.1016/j.molcel.2005.10.031
Jump up ^ Shaw G, Kamen R (August 1986), "A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation", Cell, 46 (5): 659–67, PMID 3488815, doi:10.1016/0092-8674(86)90341-7
Jump up ^ Chen, C.Y.A.; Shyu, A.B. (1995), "AU-rich elements: characterization and importance in mRNA degradation", Trends in Biochemical Sciences, 20 (11): 465–470, PMID 8578590, doi:10.1016/S0968-0004(00)89102-1
Jump up ^ Isken, O.; Maquat, L.E. (2007), "Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function", Genes & Development, 21 (15): 1833–56, PMID 17671086, doi:10.1101/gad.1566807
Jump up ^ Obbard, D.J.; Gordon, K.H.J.; Buck, A.H.; Jiggins, F.M. (2009), "The evolution of RNAi as a defence against viruses and transposable elements", Philosophical Transactions of the Royal Society B: Biological Sciences, 364 (1513): 99–115, PMC 2592633  , PMID 18926973, doi:10.1098/rstb.2008.0168
Jump up ^ Brennecke J, Stark A, Russell RB, Cohen SM (March 2005), "Principles of MicroRNA–Target Recognition", PLoS Biol., 3 (3): e85, PMC 1043860  , PMID 15723116, doi:10.1371/journal.pbio.0030085
Jump up ^ Eulalio, A.; Huntzinger, E.; Nishihara, T.; Rehwinkel, J.; Fauser, M.; Izaurralde, E. (2009), "Deadenylation is a widespread effect of miRNA regulation", RNA, 15 (1): 21–32, PMC 2612776  , PMID 19029310, doi:10.1261/rna.1399509
Jump up ^ Gregory Huang (December 6, 2012). "Moderna, $40M in Tow, Hopes to Reinvent Biotech with "Make Your Own Drug"". Xconomy.
^ Jump up to: a b Kaczmarek, JC; Kowalski, PS; Anderson, DG (27 June 2017). "Advances in the delivery of RNA therapeutics: from concept to clinical reality.". Genome medicine. 9 (1): 60. PMC 5485616  . PMID 28655327. doi:10.1186/s13073-017-0450-0.
Jump up ^ Crow, David (7 September 2017). "Moderna pledge sets investor pulses racing; Biotech group promises to rewrite rules of drug development - though sceptics say $5bn valuation is undeserved". Financial Times.
Jump up ^ Adams, Ben (September 14, 2017). "Moderna changes up R&D model, posts cancer, CV trial updates". FierceBiotech.
^ Jump up to: a b Hajj, Khalid A.; Whitehead, Kathryn A. (12 September 2017). "Tools for translation: non-viral materials for therapeutic mRNA delivery". Nature Reviews Materials. 2 (10): 17056. doi:10.1038/natrevmats.2017.56.
^ Jump up to: a b Gousseinov, Elina; Kozlov, Mikhail; Scanlan, Claire; Hammons, Aaron; Bei, Ling; Benchek, Youssef; Pirani, Karim; Pattnaik, Priyabrata; Waghmare, Ruta (September 15, 2015). "RNA-Based Therapeutics and Vaccines". Genetic Engineering News.
External links[edit]
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Life of mRNA Flash animation
RNAi Atlas: a database of RNAi libraries and their target analysis results
miRSearch: Tool for finding microRNAs that target mRNA
How mRNA is coded?: YouTube video
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