Journal ArticleDOI
Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes
TLDR
It is shown that inserting L1 sequences on a transcript significantly decreases RNA expression and therefore protein expression, andBioinformatic data are consistent with the hypothesis that L1 can serve as an evolutionary fine-tuner of the human transcriptome.Abstract:
LINE-1 (L1) elements are the most abundant autonomous retrotransposons in the human genome, accounting for about 17% of human DNA. The L1 retrotransposon encodes two proteins, open reading frame (ORF)1 and the ORF2 endonuclease/reverse transcriptase. L1 RNA and ORF2 protein are difficult to detect in mammalian cells, even in the context of overexpression systems. Here we show that inserting L1 sequences on a transcript significantly decreases RNA expression and therefore protein expression. This decreased RNA concentration does not result from major effects on the transcription initiation rate or RNA stability. Rather, the poor L1 expression is primarily due to inadequate transcriptional elongation. Because L1 is an abundant and broadly distributed mobile element, the inhibition of transcriptional elongation by L1 might profoundly affect expression of endogenous human genes. We propose a model in which L1 affects gene expression genome-wide by acting as a 'molecular rheostat' of target genes. Bioinformatic data are consistent with the hypothesis that L1 can serve as an evolutionary fine-tuner of the human transcriptome.read more
Citations
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Journal ArticleDOI
The impact of retrotransposons on human genome evolution.
Richard Cordaux,Mark A. Batzer +1 more
TL;DR: This Review focuses on non-long terminal repeat (LTR) retrotransposons, and discusses the many ways that they affect the human genome: from generating insertion mutations and genomic instability to altering gene expression and contributing to genetic innovation.
Journal ArticleDOI
Synonymous but not the same: the causes and consequences of codon bias.
Joshua B. Plotkin,Grzegorz Kudla +1 more
TL;DR: Ongoing work to quantify the dynamics of initiation and elongation is as important for understanding natural synonymous variation as it is for designing transgenes in applied contexts.
Journal ArticleDOI
Regulatory activities of transposable elements: from conflicts to benefits.
TL;DR: Recent findings supporting the long-standing hypothesis that the waves of TE invasions endured by organisms for eons have catalysed the evolution of gene-regulatory networks are reviewed.
Journal ArticleDOI
Long-range control of gene expression: emerging mechanisms and disruption in disease.
TL;DR: Functional studies have shown many of these conserved sites to be transcriptional regulatory elements that sometimes reside inside unrelated neighboring genes, such sequence-conserved elements generally harbor sites for tissue-specific DNA-binding proteins.
Journal ArticleDOI
Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition
TL;DR: It is shown that an engineered human LINE-1 element can retrotranspose in neuronal precursors derived from rat hippocampus neural stem cells, indicating that neuronal genomes might not be static, but some might be mosaic because of de novo L1 retrotransposition events.
References
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Journal ArticleDOI
Initial sequencing and analysis of the human genome.
Eric S. Lander,Lauren Linton,Bruce W. Birren,Chad Nusbaum,Michael C. Zody,Jennifer Baldwin,Keri Devon,Ken Dewar,Michael Doyle,William Fitzhugh,Roel Funke,Diane Gage,Katrina Harris,Andrew Heaford,John Howland,Lisa Kann,Jessica A. Lehoczky,Rosie Levine,Paul A. McEwan,Kevin McKernan,James Meldrim,Jill P. Mesirov,Cher Miranda,William Morris,Jerome Naylor,Christina Raymond,Mark Rosetti,Ralph Santos,Andrew Sheridan,Carrie Sougnez,Nicole Stange-Thomann,Nikola Stojanovic,Aravind Subramanian,Dudley Wyman,Jane Rogers,John Sulston,R Ainscough,Stephan Beck,David Bentley,John Burton,C M Clee,Nigel P. Carter,Alan Coulson,Rebecca Deadman,Panos Deloukas,Andrew Dunham,Ian Dunham,Richard Durbin,Lisa French,Darren Grafham,Simon G. Gregory,Tim Hubbard,Sean Humphray,Adrienne Hunt,Matthew Jones,Christine Lloyd,Amanda McMurray,Lucy Matthews,Simon Mercer,Sarah Milne,James C. Mullikin,Andrew J. Mungall,Robert W. Plumb,Mark T. Ross,Ratna Shownkeen,Sarah Sims,Robert H. Waterston,Richard K. Wilson,LaDeana W. Hillier,John Douglas Mcpherson,Marco A. Marra,Elaine R. Mardis,Lucinda Fulton,Asif T. Chinwalla,Kymberlie H. Pepin,Warren Gish,Stephanie L. Chissoe,Michael C. Wendl,Kim D. Delehaunty,Tracie L. Miner,Andrew Delehaunty,Jason B. Kramer,Lisa Cook,Robert S. Fulton,Douglas L. Johnson,Patrick Minx,Sandra W. Clifton,Trevor Hawkins,Elbert Branscomb,Paul Predki,Paul G. Richardson,Sarah Wenning,Tom Slezak,Norman A. Doggett,Jan Fang Cheng,Anne S. Olsen,Susan Lucas,Christopher J. Elkin,Edward Uberbacher,Marvin Frazier,Richard A. Gibbs,Donna M. Muzny,Steven E. Scherer,John Bouck,Erica Sodergren,Kim C. Worley,Catherine M. Rives,James H. Gorrell,Michael L. Metzker,Susan L. Naylor,Raju Kucherlapati,David L. Nelson,George M. Weinstock,Yoshiyuki Sakaki,Asao Fujiyama,Masahira Hattori,Tetsushi Yada,Atsushi Toyoda,Takehiko Itoh,Chiharu Kawagoe,Hidemi Watanabe,Yasushi Totoki,Todd D. Taylor,Jean Weissenbach,Roland Heilig,William Saurin,François Artiguenave,Philippe Brottier,Thomas Brüls,Eric Pelletier,Catherine Robert,Patrick Wincker,André Rosenthal,Matthias Platzer,Gerald Nyakatura,Stefan Taudien,Andreas Rump,Douglas R. Smith,Lynn Doucette-Stamm,Marc Rubenfield,Keith Weinstock,Mei Lee Hong,Joann Dubois,Huanming Yang,Jun Yu,Jian Wang,Guyang Huang,Jun Gu,Leroy Hood,Lee Rowen,Anup Madan,Shizen Qin,Ronald W. Davis,Nancy A. Federspiel,A. Pia Abola,Michael Proctor,Bruce A. Roe,Feng Chen,Huaqin Pan,Juliane Ramser,Hans Lehrach,Richard Reinhardt,W. Richard McCombie,Melissa De La Bastide,Neilay Dedhia,H. Blöcker,K. Hornischer,Gabriele Nordsiek,Richa Agarwala,L. Aravind,Jeffrey A. Bailey,Alex Bateman,Serafim Batzoglou,Ewan Birney,Peer Bork,Daniel G. Brown,Christopher B. Burge,Lorenzo Cerutti,Hsiu Chuan Chen,Deanna M. Church,Michele Clamp,Richard R. Copley,Tobias Doerks,Sean R. Eddy,Evan E. Eichler,Terrence S. Furey,James E. Galagan,James G. R. Gilbert,Cyrus L. Harmon,Yoshihide Hayashizaki,David Haussler,Henning Hermjakob,Karsten Hokamp,Wonhee Jang,L. Steven Johnson,Thomas A. Jones,Simon Kasif,Arek Kaspryzk,Scot Kennedy,W. James Kent,Paul Kitts,Eugene V. Koonin,Ian F Korf,David Kulp,Doron Lancet,Todd M. Lowe,Aoife McLysaght,Tarjei S. Mikkelsen,John V. Moran,Nicola Mulder,Victor J. Pollara,Chris P. Ponting,Greg Schuler,Jörg Schultz,Guy Slater,Arian F.A. Smit,Elia Stupka,Joseph Szustakowki,Danielle Thierry-Mieg,Jean Thierry-Mieg,Lukas Wagner,John W. Wallis,Raymond Wheeler,Alan Williams,Yuri I. Wolf,Kenneth H. Wolfe,Shiaw Pyng Yang,Ru Fang Yeh,Francis S. Collins,Mark S. Guyer,Jane Peterson,Adam Felsenfeld,Kris A. Wetterstrand,Richard M. Myers,Jeremy Schmutz,Mark Dickson,Jane Grimwood,David R. Cox,Maynard V. Olson,Rajinder Kaul,Christopher K. Raymond,Nobuyoshi Shimizu,Kazuhiko Kawasaki,Shinsei Minoshima,Glen A. Evans,Maria Athanasiou,Roger A. Schultz,Aristides Patrinos,Michael J. Morgan +248 more
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs
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TL;DR: The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
Journal ArticleDOI
Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: A mechanism for non-LTR retrotransposition
TL;DR: The open reading frame of the R2 element from Bombyx mori, R2Bm, in E. coli is expressed and it is shown that it encodes both sequence-specific endonuclease and reverse transcriptase activities.
Journal ArticleDOI
Human L1 Retrotransposon Encodes a Conserved Endonuclease Required for Retrotransposition
TL;DR: It is proposed that L1 EN cleaves the target site for L1 insertion and primes reverse transcription, and mutations in conserved amino acid residues of L1EN abolish its nicking activity and eliminate L1 retrotransposition.
Journal ArticleDOI
High Frequency Retrotransposition in Cultured Mammalian Cells
John V. Moran,Susan E. Holmes,Thierry Naas,Ralph J. DeBerardinis,Jef D. Boeke,Haig H. Kazazian +5 more
TL;DR: It is shown that two human L1 elements (L1.2 and LRE2) can actively retrotranspose in cultured mammalian cells, suggesting a potential role for L1-based vectors in random insertional mutagenesis.
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