Evidence map›Paper›PMID 36326816›Full record

ArticleeLife2022

Genome-wide base editor screen identifies regulators of protein abundance in yeast.

Olga T Schubert, Joshua S Bloom, Meru J Sadhu, Leonid Kruglyak

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Deconstructing cancer with precision genome editing.Biochemical Society transactions · 2024
    Review
  11. Review
  12. Article
  13. Practical Approaches for the YeastInternational journal of molecular sciences · 2023
    Review
  14. Review
  15. Article
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 2 countries.

Olga T SchubertDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, United States.ORCID 0000-0002-2613-0714
Joshua S BloomDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, United States.ORCID 0000-0002-7241-1648
Meru J SadhuDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, United States.
Leonid KruglyakDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, United States.ORCID 0000-0002-8065-3057
QB3 · US

Funding

Toward comprehensive genetic dissection of complex traits in yeastR01GM102308 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEONID KRUGLYAK · 2012 to 2026
$3.3M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM102308
6 · The paper itself

Abstract

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.

Indexed as

RNA, Guide, CRISPR-Cas SystemsSaccharomyces cerevisiaeCRISPR-Cas SystemsGenetic TestingRNA, Guide, CRISPR-Cas Systemsbase editorchromosomesCRISPR screenGAPDH isoenzymesgene expressiongene regulatory networkgeneticsgenomicsprotein regulationras/PKAS. cerevisiae

Identifiers

PMID36326816
PMCPMC9633064
OpenAlexW4308248760

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.