Evidence map›Paper›PMID 33010152›Full record

ArticleNucleic acids research2020

A genetic screen for suppressors of hyper-repression of the fission yeast PHO regulon by Pol2 CTD mutation T4A implicates inositol 1-pyrophosphates as agonists of precocious lncRNA transcription termination.

Angad Garg, Stewart Shuman, Beate Schwer

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

19 citing papers in PubMed, 32 citations in OpenAlex.

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  17. Long RNA-Mediated Chromatin Regulation in Fission Yeast and Mammals.International journal of molecular sciences · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Angad GargMolecular Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Stewart ShumanMolecular Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Beate SchwerDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.
Kettering University · USCornell University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
mRNA Capping EnzymesR01GM052470 · NIGMS · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SCHWER, BEATE, SHUMAN, STEWART H · 1995 to 2019
$9.9M
Mechanisms of DNA and RNA TransactionsR35GM126945 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Stewart H Shuman · 2018 to 2026
$8.9M
Inositol pyrophosphate dynamics affect RNA 3'-processing/transcription terminationR01GM134021 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BEATE SCHWER · 2019 to 2026
$2.8M
NCI NIH HHS P30 CA008748NIGMS NIH HHS R01 GM052470NIGMS NIH HHS R01 GM134021NIGMS NIH HHS R35 GM126945
6 · The paper itself

Abstract

Fission yeast phosphate homeostasis genes are repressed in phosphate-rich medium by transcription of upstream lncRNAs that interferes with activation of the flanking mRNA promoters. lncRNA control of PHO gene expression is influenced by the Thr4 phospho-site in the RNA polymerase II CTD and the 3' processing/termination factors CPF and Rhn1, mutations of which result in hyper-repression of the PHO regulon. Here, we performed a forward genetic screen for mutations that de-repress Pho1 acid phosphatase expression in CTD-T4A cells. Sequencing of 18 independent STF (Suppressor of Threonine Four) isolates revealed, in every case, a mutation in the C-terminal pyrophosphatase domain of Asp1, a bifunctional inositol pyrophosphate (IPP) kinase/pyrophosphatase that interconverts 5-IP7 and 1,5-IP8. Focused characterization of two STF strains identified 51 coding genes coordinately upregulated vis-à-vis the parental T4A strain, including all three PHO regulon genes (pho1, pho84, tgp1). Whereas these STF alleles-asp1-386(Stop) and asp1-493(Stop)-were lethal in a wild-type CTD background, they were viable in combination with mutations in CPF and Rhn1, in which context Pho1 was also de-repressed. Our findings implicate Asp1 pyrophosphatase in constraining 1,5-IP8 or 1-IP7 synthesis by Asp1 kinase, without which 1-IPPs can accumulate to toxic levels that elicit precocious termination by CPF/Rhn1.

Indexed as

MutationAcid PhosphataseCatalytic DomainCytoskeletal ProteinsDNA Polymerase IIGene Expression Regulation, FungalInositol PhosphatesMultifunctional EnzymesPyrophosphatasesRegulonRNA, Long NoncodingSchizosaccharomycesSchizosaccharomyces pombe ProteinsSynthetic Lethal MutationsTranscription Termination, GeneticUp-RegulationAcid Phosphataseacid phosphatase Pho1, S pombeAsp1 protein, S pombeCytoskeletal ProteinsDNA Polymerase IIinositol-1-pyrophosphateInositol PhosphatesMultifunctional EnzymesPyrophosphatasesRNA, Long NoncodingSchizosaccharomyces pombe Proteins

Identifiers

PMID33010152
PMCPMC7641756
OpenAlexW3089596143

What OpenQuestion holds

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LicenceCC BY-NC
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.