Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans
Cenik, Elif Sarinay
Byeon, Gun W.
Candille, Sophie I.
Araya, Carlos L.
Ricci, Emiliano P.
Snyder, Michael P.
UMass Chan AffiliationsRNA Therapeutics Institute
Document TypeJournal Article
MetadataShow full item record
AbstractElucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy-many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation.
SourceGenome Res. 2015 Nov;25(11):1610-21. doi: 10.1101/gr.193342.115. Epub 2015 Aug 21. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/39825
Related ResourcesLink to Article in PubMed
© 2015 Cenik et al. This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as <p>© 2015 Cenik et al. This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.</p>