Genomic variation. Impact of regulatory variation from RNA to protein

Science. 2015 Feb 6;347(6222):664-7. doi: 10.1126/science.1260793. Epub 2014 Dec 18.

Abstract

The phenotypic consequences of expression quantitative trait loci (eQTLs) are presumably due to their effects on protein expression levels. Yet the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, eQTLs tend to have significantly reduced effect sizes on protein levels, which suggests that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we identified a class of cis QTLs that affect protein abundance with little or no effect on messenger RNA or ribosome levels, which suggests that they may arise from differences in posttranslational regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Flanking Region
  • 5' Flanking Region
  • Cell Line
  • Exons
  • Gene Expression Regulation*
  • Genetic Variation*
  • Humans
  • Phenotype
  • Protein Biosynthesis / genetics*
  • Quantitative Trait Loci*
  • RNA, Messenger / genetics*
  • Ribosomes / metabolism
  • Transcription, Genetic*

Substances

  • RNA, Messenger