RT Journal Article
SR Electronic
T1 Genome-wide base editor screen identifies regulators of protein abundance in yeast
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.09.483657
DO 10.1101/2022.03.09.483657
A1 Olga T. Schubert
A1 Joshua S. Bloom
A1 Meru J. Sadhu
A1 Leonid Kruglyak
YR 2022
UL http://biorxiv.org/content/early/2022/03/09/2022.03.09.483657.abstract
AB Abundance of proteins is extensively regulated both transcriptionally and post-transcriptionally. To systematically characterize how regulation of protein abundance is encoded in the genome and identify protein regulators on a genome-wide scale, we developed a genetic screen that uses a CRISPR base editor. We examined the effects of 16,452 genetic perturbations on the abundance of eleven yeast proteins representing a variety of cellular functions. Thereby, we uncovered hundreds of regulatory relationships, including a novel link between the GAPDH isoenzymes Tdh1/2/3 and the Ras/PKA pathway. Many of the identified regulators are specific to one of the eleven proteins, but we also found genes that, upon perturbation, affected the abundance of most of the tested proteins. While the more specific regulators usually act transcriptionally, broad regulators often have roles in protein translation. Our results provide unprecedented insights into the components, scale and connectedness of the protein regulatory network.Competing Interest StatementThe authors have declared no competing interest.