Environmental perturbations lead to extensive directional shifts in RNA processing
Publication Date
October 12, 2017
Authors
Allison L. Richards, Donovan Watza, Anthony Findley, Adnan Alazizi, et al
Volume
13
Issue
10
Pages
e1006995
DOI
https://dx.plos.org/10.1371/journal.pgen.1006995
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1006995
Scopus
85033220743
Mendeley
http://www.mendeley.com/research/environmental-perturbations-lead-extensive-directional-shifts-rna-processing
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Mendeley | Further Information

{"title"=>"Environmental perturbations lead to extensive directional shifts in RNA processing", "type"=>"journal", "authors"=>[{"first_name"=>"Allison L.", "last_name"=>"Richards", "scopus_author_id"=>"44161465300"}, {"first_name"=>"Donovan", "last_name"=>"Watza", "scopus_author_id"=>"56455301200"}, {"first_name"=>"Anthony", "last_name"=>"Findley", "scopus_author_id"=>"57196437199"}, {"first_name"=>"Adnan", "last_name"=>"Alazizi", "scopus_author_id"=>"57197794095"}, {"first_name"=>"Xiaoquan", "last_name"=>"Wen", "scopus_author_id"=>"8846776400"}, {"first_name"=>"Athma A.", "last_name"=>"Pai", "scopus_author_id"=>"35366984200"}, {"first_name"=>"Roger", "last_name"=>"Pique-Regi", "scopus_author_id"=>"14619610700"}, {"first_name"=>"Francesca", "last_name"=>"Luca", "scopus_author_id"=>"23969329700"}], "year"=>2017, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"619157951", "doi"=>"10.1371/journal.pgen.1006995", "issn"=>"15537404", "scopus"=>"2-s2.0-85033220743", "sgr"=>"85033220743", "isbn"=>"1111111111"}, "id"=>"4d779ad9-3d2b-38a2-ba41-5a438509fa16", "abstract"=>"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 ELF2 and other factors in the ETS family. We also performed AFE QTL mapping in 373 individuals and found an enrichment for SNPs predicted to disrupt binding of the ELF2 factor. Together, these results demonstrate that RNA processing is dramatically changed in response to environmental perturbations through specific mechanisms regulated by trans factors.", "link"=>"http://www.mendeley.com/research/environmental-perturbations-lead-extensive-directional-shifts-rna-processing", "reader_count"=>20, "reader_count_by_academic_status"=>{"Researcher"=>4, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1, "Lecturer"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Researcher"=>4, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1, "Lecturer"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>1, "Computer Science"=>2, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Environmental Science"=>{"Environmental Science"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>2}

Scopus | Further Information

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