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Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans [preprint]

Cenik, Can
Cenik, Elif Sarinay
Byeon, Gun W.
Grubert, Fabian
Candille, Sophie I.
Spacek, Damek
Alsallakh, Bilal
Tilgner, Hagen
Araya, Carlos L.
Tang, Hua
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Authors
Cenik, Can
Cenik, 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.
Student Authors
Faculty Advisor
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UMass Chan Affiliations
Document Type
Preprint
Publication Date
2015-04-26
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Abstract

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.

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DOI
10.1101/018572
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Now published in Genome Research doi: 10.1101/gr.193342.115.

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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.