Proteomics

Dataset Information

119

Impact of Regulatory Variation from RNA to Protein


ABSTRACT: Genetic variants that impact gene regulation are important contributors to human phenotypic variation. For this reason, considerable efforts have been made to identify genetic associations with differences in mRNA levels of nearby genes, namely, cis expression quantitative trait loci (eQTLs). The phenotypic consequences of eQTLs are presumably due, in most cases, to their ultimate effects on protein expression levels. Yet, only few studies have quantified the impact of genetic variation on proteins levels directly. It remains unclear how faithfully eQTLs are reflected at the protein level, and whether there is a significant layer of cis regulatory variation acting primarily on translation or steady state protein levels. To address these questions, we measured ribosome occupancy by high-throughput sequencing, and relative protein levels by high-resolution quantitative mass spectrometry, in a panel of lymphoblastoid cell lines (LCLs) in which we had previously measured transcript expression using RNA sequencing. We then mapped genetic variants that are associated with changes in transcript expression (eQTLs), ribosome occupancy (rQTLs), or protein abundance (pQTLs). Most of the QTLs we detected are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, we found that eQTLs tend to have significantly reduced effect sizes on protein levels, suggesting that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we confirmed the presence of a class of cis QTLs that specifically affect protein abundance with little or no effect on mRNA levels; most of these QTLs have little effect on ribosome occupancy, and hence may arise from differences in post-translational regulation.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo sapiens  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Disease Free

SUBMITTER: Zia Khan  

LAB HEAD: Yoav Gilad

PROVIDER: PXD001406 | Pride | 2014-12-19

REPOSITORIES: Pride

Similar Datasets

2014-12-19 | E-GEOD-61742 | ArrayExpress
2015-02-14 | E-GEOD-65912 | ArrayExpress
2014-05-09 | E-GEOD-57471 | ArrayExpress
2010-08-19 | E-GEOD-9703 | ArrayExpress
2011-10-28 | E-GEOD-33321 | ArrayExpress
| GPM11210033257 | GPMDB
| GPM32320005946 | GPMDB
2012-08-27 | E-GEOD-33154 | ArrayExpress
2017-05-18 | MODEL1511170001 | BioModels
2017-05-18 | MODEL1511170002 | BioModels