Differences in protein abundance explained by mRNA levels

Range 56 - 84 %
Organism Mouse Mus musculus
Reference Li et al. (2014), System wide analyses have underestimated protein abundances and the importance of transcription in mammals. PeerJ 2:e270 DOI 10.7717/peerj.270 abstract & p.16 2nd paragraphPubMed ID24688849
Primary Source Schwanhausser et al., 2011. Global quantification of mammalian gene expression control. Nature 473: 337–342 DOI 10.1038/nature10098.PubMed ID21593866
Method "Using individual measurements for 61 housekeeping proteins to rescale whole proteome data from Schwanhausser et al. (2011 primary source), [researchers] find that the median protein detected is expressed at 170,000 molecules per cell and that [their] corrected protein abundance estimates show a higher correlation with mRNA abundances than do the uncorrected protein data. In addition, [researchers] estimated the impact of further errors in mRNA and protein abundances using direct experimental measurements of these errors. The resulting analysis suggests that mRNA levels explain at least 56% of the differences in protein abundance for the 4,212 genes detected by Schwanhausser et al. (2011 primary source), though because one major source of error could not be estimated the true percent contribution should be higher. [Researchers] also employed a second, independent strategy to determine the contribution of mRNA levels to protein expression. [Researchers] show that the variance in translation rates directly measured by ribosome profiling is only 9% of that inferred by Schwanhausser et al. (2011 primary source), and that the measured and inferred translation rates correlate poorly (R^2 = 0.14). Based on this, [researchers'] second strategy suggests that mRNA levels explain ~84% of the variance in protein levels."
Comments Please note-"By measuring mRNA degradation and protein degradation rates as well, the rates of transcription and translation can be additionally inferred indirectly. Using this approach to study mouse NIH3T3 fibroblasts, Schwanhausser et al. (2011 primary source) concluded that mRNA levels explain ~40% of the variability in protein levels. That the cellular abundance of proteins is predominantly controlled at the level of translation. That transcription is the second largest determinant. And that the degradation of mRNAs and proteins play a significant but lesser role." "...[researchers] estimate that mRNA abundance explains 56%–84% for a set of 4,212 detected proteins." Primary source: "[Researchers] used parallel metabolic pulse labelling with amino acids and 4sU to measure simultaneously protein and mRNA turnover in a population of exponentially growing non-synchronized NIH3T3 mouse fibroblasts (Fig. 1a)"
Entered by Uri M
ID 111364