Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans
Authors
Cenik, CanCenik, Elif Sarinay
Byeon, Gun W.
Grubert, Fabian
Candille, Sophie I.
Spacek, Damek
Alsallakh, Bilal
Tilgner, Hagen
Araya, Carlos L.
Tang, Hua
Ricci, Emiliano P.
Snyder, Michael P.
UMass Chan Affiliations
RNA Therapeutics InstituteDocument Type
Journal ArticlePublication Date
2015-11-01
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Elucidating 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.Source
Genome Res. 2015 Nov;25(11):1610-21. doi: 10.1101/gr.193342.115. Epub 2015 Aug 21. Link to article on publisher's siteDOI
10.1101/gr.193342.115Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39825PubMed ID
26297486Related Resources
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© 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/.
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http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/gr.193342.115
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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>