Non‐coding RNAs: regulators of disease
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TLDR
The biology of ncRNAs is reviewed, focusing on the fundamental mechanisms by which nc RNAs facilitate normal development and physiology and, when dysfunctional, underpin disease, and the need to move beyond the confines of protein‐coding genes.Abstract:
For 50 years the term 'gene' has been synonymous with regions of the genome encoding mRNAs that are translated into protein. However, recent genome-wide studies have shown that the human genome is pervasively transcribed and produces many thousands of regulatory non-protein-coding RNAs (ncRNAs), including microRNAs, small interfering RNAs, PIWI-interacting RNAs and various classes of long ncRNAs. It is now clear that these RNAs fulfil critical roles as transcriptional and post-transcriptional regulators and as guides of chromatin-modifying complexes. Here we review the biology of ncRNAs, focusing on the fundamental mechanisms by which ncRNAs facilitate normal development and physiology and, when dysfunctional, underpin disease. We also discuss evidence that intergenic regions associated with complex diseases express ncRNAs, as well as the potential use of ncRNAs as diagnostic markers and therapeutic targets. Taken together, these observations emphasize the need to move beyond the confines of protein-coding genes and highlight the fact that continued investigation of ncRNA biogenesis and function will be necessary for a comprehensive understanding of human disease.read more
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References
More filters
Journal ArticleDOI
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Andrew Fire,SiQun Xu,Mary K. Montgomery,Steven A. Kostas,Steven A. Kostas,Samuel E. Driver,Craig C. Mello +6 more
TL;DR: To their surprise, it was found that double-stranded RNA was substantially more effective at producing interference than was either strand individually, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
Journal ArticleDOI
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
TL;DR: 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.
Journal ArticleDOI
MicroRNA expression profiles classify human cancers
Jun Lu,Gad Getz,Eric A. Miska,Eric A. Miska,Ezequiel Alvarez-Saavedra,Justin Lamb,David Peck,Alejandro Sweet-Cordero,Alejandro Sweet-Cordero,Benjamin L. Ebert,Benjamin L. Ebert,Raymond H. Mak,Raymond H. Mak,Adolfo A. Ferrando,James R. Downing,Tyler Jacks,H. Robert Horvitz,H. Robert Horvitz,Todd R. Golub,Todd R. Golub,Todd R. Golub +20 more
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Journal ArticleDOI
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
Ewan Birney,John A. Stamatoyannopoulos,Anindya Dutta,Roderic Guigó,Thomas R. Gingeras,Elliott H. Margulies,Zhiping Weng,Michael Snyder,Emmanouil T. Dermitzakis,Robert E. Thurman,Michael S. Kuehn,Christopher M. Taylor,Shane Neph,Christoph M. Koch,Saurabh Asthana,Ankit Malhotra,Ivan Adzhubei,Jason A. Greenbaum,Robert M. Andrews,Paul Flicek,Patrick J. Boyle,Hua Cao,Nigel P. Carter,Gayle K. Clelland,Sean Davis,Nathan Day,Pawandeep Dhami,Shane C. Dillon,Michael O. Dorschner,Heike Fiegler,Paul G. Giresi,Jeff Goldy,Michael Hawrylycz,Andrew Haydock,Richard Humbert,Keith D. James,Brett E. Johnson,Ericka M. Johnson,Tristan Frum,Elizabeth Rosenzweig,Neerja Karnani,Kirsten Lee,Gregory Lefebvre,Patrick A. Navas,Fidencio Neri,Stephen C. J. Parker,Peter J. Sabo,Richard Sandstrom,Anthony Shafer,David Vetrie,Molly Weaver,Sarah Wilcox,Man Yu,Francis S. Collins,Job Dekker,Jason D. Lieb,Thomas D. Tullius,Gregory E. Crawford,Shamil R. Sunyaev,William Stafford Noble,Ian Dunham,Alexandre Reymond,Alexandre Reymond,Philipp Kapranov,Joel Rozowsky,Deyou Zheng,Robert Castelo,Adam Frankish,Jennifer Harrow,Srinka Ghosh,Albin Sandelin,Ivo L. Hofacker,Robert Baertsch,Damian Keefe,Sujit Dike,Jill Cheng,Heather A. Hirsch,Edward A. Sekinger,Julien Lagarde,Josep F. Abril,Josep F. Abril,Atif Shahab,Christoph Flamm,Christoph Flamm,Claudia Fried,Jörg Hackermüller,Jana Hertel,Manja Lindemeyer,Kristin Missal,Andrea Tanzer,Andrea Tanzer,Stefan Washietl,Jan O. Korbel,Olof Emanuelsson,Jakob Skou Pedersen,Nancy Holroyd,Ruth Taylor,David Swarbreck,Nicholas Matthews,Mark Dickson,Daryl J. Thomas,Matthew T. Weirauch,James G. R. Gilbert,Jorg Drenkow,Ian Bell,Xiaodong Zhao,Kandhadayar G. Srinivasan,Wing-Kin Sung,Hong Sain Ooi,Kuo Ping Chiu,Sylvain Foissac,Tyler Alioto,Michael R. Brent,Lior Pachter,Michael L. Tress,Alfonso Valencia,Siew Woh Choo,Chiou Yu Choo,Catherine Ucla,Caroline Manzano,Carine Wyss,Evelyn Cheung,Taane G. Clark,James B. Brown,Madhavan Ganesh,Sandeep Patel,Hari Tammana,Jacqueline Chrast,Charlotte N. Henrichsen,Chikatoshi Kai,Jun Kawai,Ugrappa Nagalakshmi,Jia Qian Wu,Zheng Lian,Jin Lian,Peter E. Newburger,Xueqing Zhang,Peter J. Bickel,John S. Mattick,Piero Carninci,Yoshihide Hayashizaki,Sherman M. Weissman,Tim Hubbard,Richard M. Myers,Jane Rogers,Peter F. Stadler,Peter F. Stadler,Peter F. Stadler,Todd M. Lowe,Chia-Lin Wei,Yijun Ruan,Kevin Struhl,Mark Gerstein,Stylianos E. Antonarakis,Yutao Fu,Eric D. Green,Ulas Karaoz,Adam Siepel,Adam Siepel,James Taylor,Laura A. Liefer,Kris A. Wetterstrand,Peter J. Good,Elise A. Feingold,Mark S. Guyer,Gregory M. Cooper,Gregory M. Cooper,George Asimenos,Colin N. Dewey,Minmei Hou,Sergey Nikolaev,Juan I. Montoya-Burgos,Ari Löytynoja,Simon Whelan,Fabio Pardi,Tim Massingham,Haiyan Huang,Nan Zhang,Nan Zhang,Ian Holmes,James C. Mullikin,Abel Ureta-Vidal,Benedict Paten,Michael Seringhaus,Deanna M. Church,Kate R. Rosenbloom,W. James Kent,Eric A. Stone,Serafim Batzoglou,Nick Goldman,Ross C. Hardison,David Haussler,Webb Miller,Arend Sidow,Nathan D. Trinklein,Zhengdong D. Zhang,Leah O. Barrera,Rhona K. Stuart,David C. King,Adam Ameur,Stefan Enroth,Mark Bieda,Jonghwan Kim,Akshay Bhinge,Nan Jiang,Jun Liu,Fei Yao,Vinsensius B. Vega,Charlie W.H. Lee,Patrick Ng,Annie Yang,Zarmik Moqtaderi,Zhou Zhu,Xiaoqin Xu,Sharon L. Squazzo,Matthew J. Oberley,David R. Inman,Michael A. Singer,Todd Richmond,Kyle J. Munn,Kyle J. Munn,Alvaro Rada-Iglesias,Ola Wallerman,Jan Komorowski,Joanna C. Fowler,Phillippe Couttet,Alexander W. Bruce,Oliver M. Dovey,Peter D. Ellis,Cordelia Langford,David A. Nix,Ghia Euskirchen,Stephen Hartman,Alexander E. Urban,Peter Kraus,Sara Van Calcar,Nate Heintzman,Tae Hoon Kim,Kun Wang,Chunxu Qu,Gary C. Hon,Rosa Luna,Christopher K. Glass,M. Geoff Rosenfeld,Shelley Force Aldred,Sara J. Cooper,Anason S. Halees,Jane M. Lin,Hennady P. Shulha,Xiaoling Zhang,Mousheng Xu,Jaafar N. Haidar,Yong Yu,Vishwanath R. Iyer,Roland Green,Claes Wadelius,Peggy J. Farnham,Bing Ren,Rachel A. Harte,Angie S. Hinrichs,Heather Trumbower,Hiram Clawson,Jennifer Hillman-Jackson,Ann S. Zweig,Kayla E. Smith,Archana Thakkapallayil,Galt P. Barber,Robert M. Kuhn,Donna Karolchik,Lluís Armengol,Christine P. Bird,Paul I.W. de Bakker,Andrew D. Kern,Nuria Lopez-Bigas,Joel D. Martin,Barbara E. Stranger,Abigail Woodroffe,Eugene Davydov,Antigone S. Dimas,Eduardo Eyras,Ingileif B. Hallgrímsdóttir,Julian L. Huppert,Michael C. Zody,Gonçalo R. Abecasis,Xavier Estivill,Gerard G. Bouffard,Xiaobin Guan,Nancy F. Hansen,Jacquelyn R. Idol,Valerie Maduro,Baishali Maskeri,Jennifer C. McDowell,Morgan Park,Pamela J. Thomas,Alice C. Young,Robert W. Blakesley,Donna M. Muzny,Erica Sodergren,David A. Wheeler,Kim C. Worley,Huaiyang Jiang,George M. Weinstock,Richard A. Gibbs,Tina Graves,Robert S. Fulton,Elaine R. Mardis,Richard K. Wilson,Michele Clamp,James Cuff,Sante Gnerre,David B. Jaffe,Jean L. Chang,Kerstin Lindblad-Toh,Eric S. Lander,Eric S. Lander,Maxim Koriabine,Mikhail Nefedov,Kazutoyo Osoegawa,Yuko Yoshinaga,Baoli Zhu,Pieter J. de Jong +320 more
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Journal ArticleDOI
Long non-coding RNAs: insights into functions
TL;DR: The rapidly advancing field of long ncRNAs is reviewed, describing their conservation, their organization in the genome and their roles in gene regulation, and the medical implications.
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