1. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.
- Author
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Cenik C, Cenik ES, Byeon GW, Grubert F, Candille SI, Spacek D, Alsallakh B, Tilgner H, Araya CL, Tang H, Ricci E, and Snyder MP
- Subjects
- Chromatin genetics, Chromatin metabolism, Gene Expression Profiling, Gene Expression Regulation, Humans, Proteomics, Quantitative Trait Loci, RNA, Messenger genetics, RNA, Messenger metabolism, Ribosomes genetics, Ribosomes metabolism, Sequence Alignment, Sequence Analysis, RNA, Polymorphism, Single Nucleotide, Protein Biosynthesis, RNA metabolism
- 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., (© 2015 Cenik et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2015
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