Proteome-wide effects of single gene perturbations

Protein expression levels are controlled at the transcriptional, translational and post-translational level and their regulatory principles are starting to emerge. While transcriptional outcomes, which are commonly also used as a proxy for protein abundance, have been investigated on a larger scale, the study of translational output requires large-scale proteomics data. However, data for proteome alterations by systematic assessment of knockouts genome-wide is not available yet. We here determined the individual proteome changes for 3,308 non-essential genes in the yeast S. pombe. We observed that genes with high proteome remodeling are predominantly involved in gene expression regulation, in particular acting as translational regulators. Focusing on those knockout strains with a large number of altered proteins, we performed paired transcriptome/proteome measurements to uncover translational regulators and features of translational regulation. Furthermore, by similarity clustering of these proteome changes, we infer gene functionality that can be extended to other species such as human or baker’s yeast.