Alternative isoform regulation in human tissue transcriptomes

Nature
Eric T WangChristopher B Burge

Abstract

Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing, 86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a ...Continue Reading

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Jun 14, 2013·BMC Bioinformatics·Li Song, Liliana Florea
Jun 30, 2009·BMC Evolutionary Biology·Ramil N NurtdinovMikhail Gelfand
Feb 25, 2010·BMC Genetics·Tiffany BrunsonQing Song
Apr 18, 2009·BMC Genomics·Alissa M ReschEugene V Koonin
Nov 6, 2009·BMC Genomics·Alexander ChurbanovChindo Hicks
Jan 31, 2009·BMC Genomics·Anna WetterbomTomas F Bergström
Jun 23, 2010·BMC Genomics·Ashish AgarwalMark B Gerstein
Jun 25, 2010·BMC Genomics·Timothée RevilLoydie A Jerome-Majewska
Oct 6, 2010·BMC Genomics·Federico ZambelliGraziano Pesole
Dec 4, 2010·BMC Genomics·Daniel KlevebringJoakim Lundeberg
Dec 21, 2010·BMC Genomics·Wen Huang, Hasan Khatib
Dec 21, 2010·BMC Genomics·Shengrong LinKara Juneau
Dec 22, 2010·BMC Genomics·Yizhen JiaDavid K Smith
Nov 10, 2011·BMC Genomics·Anna Esteve-CodinaMiguel Pérez-Enciso
Mar 28, 2012·BMC Genomics·Jinsil KimYi Xing
Mar 6, 2012·BMC Genomics·Gloria C-L Fu, Wen-Chang Lin
Mar 20, 2013·BMC Genomics·Inka SastallaMahtab Moayeri
Sep 11, 2013·BMC Genomics·Dechassa DuressaSteven J Klosterman
May 10, 2011·BMC Molecular Biology·Danielle CassJ Andrew Berglund
Jul 11, 2012·BMC Plant Biology·Hai DuYi-Xiong Tang
Jun 29, 2011·BMC Pulmonary Medicine·Christina Orsmark PietrasJuha Kere
Aug 6, 2010·BMC Structural Biology·RyangGuk Kim, Jun-tao Guo
Dec 31, 2011·Journal of Translational Medicine·Karen K MestanSimon Lin
Oct 6, 2011·EURASIP Journal on Bioinformatics & Systems Biology·Dorothea EmigMario Albrecht
Apr 18, 2009·Biology Direct·Alicia Oshlack, Matthew J Wakefield
Apr 21, 2011·Algorithms for Molecular Biology : AMB·Marius NicolaeAlex Zelikovsky
Oct 12, 2012·BMC Systems Biology·Chao DaiXianghong Jasmine Zhou
Jun 14, 2013·BMC Medical Genomics·Poornima Bhat-NakshatriHarikrishna Nakshatri
Nov 28, 2012·Journal of Clinical Bioinformatics·Subhashini SrinivasanRaghunathan Srivatsan
Jan 24, 2009·Genome Biology·Sabine MildeThomas C G Bosch
Mar 31, 2009·Genome Biology·Olivier HarismendyKelly A Frazer
Feb 6, 2010·Genome Biology·Matthew D YoungAlicia Oshlack
Mar 4, 2010·Genome Biology·Mark D Robinson, Alicia Oshlack
Mar 13, 2010·Genome Biology·Can CenikFrederick P Roth
Mar 20, 2010·Genome Biology·Adam AmeurUlf Gyllensten
May 13, 2010·Genome Biology·Jun LiWing Hung Wong
Jan 22, 2011·Genome Biology·Guido LeoniAnna Tramontano
Feb 18, 2011·Genome Biology·Li YangLing-Ling Chen
Mar 18, 2011·Genome Biology·Adam RobertsLior Pachter
Aug 27, 2011·Genome Biology·Andrea SbonerMark B Gerstein
Jun 23, 2012·Genome Biology·Nicholas J McGlincyJernej Ule
Jan 31, 2013·Genome Biology·Jong Kyoung Kim, John C Marioni
Mar 30, 2013·Genome Biology·Nicolas PhilippeEric Rivals
Dec 25, 2012·Genome Medicine·Sebastian BoegelUgur Sahin
Mar 29, 2012·RNA·Nicole M MartinezKristen W Lynch
Aug 7, 2009·RNA·Amy Pandya-Jones, Douglas L Black
Dec 30, 2009·RNA·Jean-Philippe BrosseauSherif Abou Elela
Nov 21, 2009·RNA·Jean-François FisetteBenoit Chabot
Dec 17, 2009·RNA·Jeremy E Wilusz, David L Spector
Aug 20, 2010·RNA·Adonis SkandalisMiriam H Richards
May 27, 2010·PLoS Biology·Harm van BakelTimothy R Hughes
Jan 12, 2012·PLoS Biology·Robert K BradleyChristopher B Burge
Oct 31, 2009·PLoS Computational Biology·Donna K Slonim, Itai Yanai
Nov 18, 2009·PLoS Computational Biology·Gary HonBing Ren
Dec 17, 2009·PLoS Computational Biology·Daniel RamsköldRickard Sandberg
Mar 3, 2012·PLoS Computational Biology·Purvesh KhatriAtul J Butte
Apr 13, 2012·PLoS Computational Biology·Onur SakaryaAsim S Siddiqui
Jul 23, 2013·PLoS Computational Biology·Natalia PietrosemoliPeter Tompa