Extensive post-transcriptional regulation across human tissues

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 and (ii) the factors determining the physiological variability of the same protein across different tissue types. We estimated the factors determining these two orthogonal sources of variability and found that mRNA levels can account for most of the variability between the levels of different proteins but not for the protein variability across tissue-types. After accounting for measurement noise, most of the across-tissue protein variability remains unexplained by mRNA levels, suggesting extensive post-transcriptional regulation. These results reconcile existing estimates in the literature, caution against estimating protein fold-changes from mRNA fold-changes between different cell-types, and highlight the contribution of post-transcriptional regulation in shaping tissue-type-specific proteomes. 1 . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/020206 doi: bioRxiv preprint first posted online May. 31, 2015;