PXD029363

PXD029363 is an original dataset announced via ProteomeXchange.

Title	Genome-wide base editor screen identifies regulators of protein abundance in yeast
Description	Proteins are key molecular players in a cell, and their abundance is extensively regulated not just at the level of gene expression but also post-transcriptionally. Here, we describe a genetic screen in yeast that enables systematic characterization of how protein abundance regulation is encoded in the genome. The screen combines a CRISPR/Cas9 base editor to introduce point mutations with fluorescent tagging of endogenous proteins to facilitate a flow-cytometric readout. We first benchmarked base editor performance in yeast with individual gRNAs as well as in positive and negative selection screens. We then examined the effects of 16,452 genetic perturbations on the abundance of eleven proteins representing a variety of cellular functions. 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. Overall, our novel screening approach provides unprecedented insights into the components, scale and connectedness of the protein regulatory network.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:57:32.729.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029363
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Olga T. Schubert
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-26 22:55:57	ID requested
1	2022-11-07 12:02:53	announced
⏵ 2	2023-11-14 07:57:33	announced	2023-11-14: Updated project metadata.

10.6019/PXD029363;

Schubert OT, Bloom JS, Sadhu MJ, Kruglyak L, Genome-wide base editor screen identifies regulators of protein abundance in yeast. Elife, 11():(2022) [pubmed]

submitter keyword: LC-MSMS,Yeast

Leonid Kruglyak
contact affiliation	University of California, Los Angeles, United States
contact email	lkruglyak@mednet.ucla.edu
lab head
Olga T. Schubert
contact affiliation	ETH Zurich
contact email	olga.schubert@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029363
     1. Label: PRIDE project
     2. Name: Genome-wide base editor screen identifies regulators of protein abundance in yeast