RT Journal Article
SR Electronic
T1 Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 018572
DO 10.1101/018572
A1 Can Cenik
A1 Elif Sarinay Cenik
A1 Gun W. Byeon
A1 Fabian Grubert
A1 Sophie I Candille
A1 Damek Spacek
A1 Bilal Alsallakh
A1 Hagen Tilgner
A1 Carlos L. Araya
A1 Hua Tang
A1 Emiliano Ricci
A1 Michael P. Snyder
YR 2015
UL http://biorxiv.org/content/early/2015/04/26/018572.abstract
AB 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.