Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans [preprint]
Cenik, Elif Sarinay
Byeon, Gun W.
Candille, Sophie I.
Araya, Carlos L.
Ricci, Emiliano P.
Snyder, Michael P.
UMass Chan AffiliationsRNA Therapeutics Institute
lymphoblastoid cell lines
personalized gene expression control
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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.
bioRxiv 018572; doi: https://doi.org/10.1101/018572. Link to preprint on bioRxiv service.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29345
Now published in Genome Research doi: 10.1101/gr.193342.115.
RightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.