Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans [preprint]
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
PreprintPublication Date
2015-04-26Keywords
genomicsRNA
personalized medicine
lymphoblastoid cell lines
personalized gene expression control
ribosome occupancy
Computational Biology
Genetic Phenomena
Genomics
Investigative Techniques
Metadata
Show full item recordAbstract
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
bioRxiv 018572; doi: https://doi.org/10.1101/018572. Link to preprint on bioRxiv service.
DOI
10.1101/018572Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29345Related Resources
Now published in Genome Research doi: 10.1101/gr.193342.115.
Rights
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/018572
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.