RT Journal Article SR Electronic T1 Post-transcriptional regulation across human tissues JF bioRxiv FD Cold Spring Harbor Laboratory SP 020206 DO 10.1101/020206 A1 Alexander Franks A1 Edoardo Airoldi A1 Nikolai Slavov YR 2016 UL http://biorxiv.org/content/early/2016/10/06/020206.abstract AB Transcriptional and post-transcriptional regulation shape tissue-type-specific proteomes, but their relative contributions remain contested. Estimates of the factors determining protein levels in human tissues do not distinguish between (i) the factors determining the variability between the abundances of different proteins, i.e., mean-level-variability and, (ii) the factors determining the physiological variability of the same protein across different tissue types, i.e., across-tissue variability. We sought to estimate the contribution of transcript levels to these two orthogonal sources of variability, and found that mRNA levels can account for most of the mean-level-variability but not for across-tissue variability. The precise quantification of the latter estimate is limited by substantial measurement noise. However, protein-to-mRNA ratios exhibit substantial across-tissue variability that is functionally concerted and reproducible across different datasets, suggesting extensive post-transcriptional regulation. These results caution against estimating protein fold-changes from mRNA fold-changes between different cell-types, and highlight the contribution of post-transcriptional regulation to shaping tissue-type-specific proteomes.