Environmental perturbations lead to extensive directional shifts in RNA processing

PLoS Genetics
Allison L RichardsFrancesca Luca


Environmental perturbations have large effects on both organismal and cellular traits, including gene expression, but the extent to which the environment affects RNA processing remains largely uncharacterized. Recent studies have identified a large number of genetic variants associated with variation in RNA processing that also have an important role in complex traits; yet we do not know in which contexts the different underlying isoforms are used. Here, we comprehensively characterized changes in RNA processing events across 89 environments in five human cell types and identified 15,300 event shifts (FDR = 15%) comprised of eight event types in over 4,000 genes. Many of these changes occur consistently in the same direction across conditions, indicative of global regulation by trans factors. Accordingly, we demonstrate that environmental modulation of splicing factor binding predicts shifts in intron retention, and that binding of transcription factors predicts shifts in alternative first exon (AFE) usage in response to specific treatments. We validated the mechanism hypothesized for AFE in two independent datasets. Using ATAC-seq, we found altered binding of 64 factors in response to selenium at sites of AFE shift, including ...Continue Reading


Sep 13, 2000·The Journal of Allergy and Clinical Immunology·P ChristodoulopoulosQ A Hamid
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·El Chérif IbrahimTom Maniatis
May 29, 2007·Nucleic Acids Research·Christina BackesHans-Peter Lenhof
Nov 4, 2008·Nature·Eric T WangChristopher B Burge
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Matjaz BarboricB Matija Peterlin
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Oct 26, 2010·The Journal of Clinical Investigation·Rachel Wilson GoeheCharles E Chalfant
Nov 9, 2010·Nature Methods·Yarden KatzChristopher B Burge
Apr 21, 2012·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·A H PoonQ Hamid
Sep 4, 2012·Nature Genetics·Elin GrundbergMultiple Tissue Human Expression Resource (MuTHER) Consortium
Sep 8, 2012·Nature·ENCODE Project Consortium
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Dec 25, 2012·The Canadian Journal of Cardiology·Philip G JosephSonia S Anand
Jun 19, 2013·Nature Reviews. Genetics·Ran ElkonReuven Agami
Jul 13, 2013·Nature·Debashish RayTimothy R Hughes
Aug 16, 2013·Current Opinion in Allergy and Clinical Immunology·Y Bossé
Sep 17, 2013·Nature·Tuuli LappalainenEmmanouil T Dermitzakis
Mar 22, 2014·BMC Medical Genomics·Qu ZhangSitong Sheng
Nov 21, 2014·American Journal of Respiratory and Critical Care Medicine·Po-Jui ChangPankaj K Bhavsar
Dec 2, 2014·Nature Genetics·Alfonso BuilEmmanouil T Dermitzakis
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 31, 2015·PLoS Genetics·Maria Gutierrez-ArcelusEmmanouil T Dermitzakis
Feb 20, 2015·Nature·Roadmap Epigenomics ConsortiumManolis Kellis
Jun 18, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yafang LiChristopher I Amos
Jun 27, 2015·Genome Medicine·Heidi Dvinge, Robert K Bradley
Oct 3, 2015·American Journal of Human Genetics·Halit Ongen, Emmanouil T Dermitzakis
Oct 21, 2015·Genomics Data·Mitchell K P LaiMichelle G K Tan
Oct 30, 2015·Scientific Reports·Gregory A MoyerbraileanFrancesca Luca
Feb 24, 2016·PLoS Genetics·Gregory A MoyerbraileanRoger Pique-Regi
Apr 30, 2016·Science·Yang I LiJonathan K Pritchard
May 26, 2016·Advances in Biological Regulation·Shahram Bahrami, Finn Drabløs
Oct 1, 2016·Cell Death and Differentiation·Maria Paola ParonettoClaudio Sette
Oct 1, 2016·International Journal of Molecular Sciences·Hanna KędzierskaAgnieszka Piekiełko-Witkowska
Nov 2, 2016·Current Opinion in Pulmonary Medicine·Manali MukherjeeParameswaran Nair
Dec 6, 2016·Nature Genetics·Daria V ZhernakovaLude Franke
Dec 10, 2016·Genome Research·Gregory A MoyerbraileanFrancesca Luca
Jan 12, 2017·International Journal of Epidemiology·Jessica TyrrellTimothy M Frayling


Feb 24, 2018·International Journal of Molecular Sciences·Chi-Ming WongMabel Yin-Chun Yau
Feb 21, 2020·The International Journal of Neuroscience·Abhilash LudhiadchAnjana Munshi
Apr 13, 2019·Nature Communications·Maxime RotivalLluis Quintana-Murci
Feb 10, 2021·Zoology : Analysis of Complex Systems, ZACS·Mathilde CordellierEric von Elert
Feb 11, 2021·Cell & Bioscience·Jiyu DingBingli Wu
Dec 24, 2018·Trends in Microbiology·Usama AshrafNadia Naffakh

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