Evidence map›Paper›PMID 25883047›Full record

ArticleRNA (New York, N.Y.)2015

Genetic and structural analysis of the essential fission yeast RNA polymerase II CTD phosphatase Fcp1.

Beate Schwer, Agnidipta Ghosh, Ana M Sanchez, Christopher D Lima, Stewart Shuman

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.2field-weighted citation impact, top 43% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
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

5 authors at 3 institutions in 1 country.

Beate SchwerMicrobiology and Immunology Department, Weill Cornell Medical College, New York, New York 10065, USA.
Agnidipta GhoshStructural Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA.
Ana M SanchezMicrobiology and Immunology Department, Weill Cornell Medical College, New York, New York 10065, USA.
Christopher D LimaStructural Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA Howard Hughes Medical Institute, Sloan-Kettering Institute, New York, New York 10065, USA.
Stewart ShumanMolecular Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA.
Cornell University · USKettering University · USHoward Hughes Medical Institute · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
mRNA Capping EnzymesR01GM052470 · NIGMS · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SCHWER, BEATE, SHUMAN, STEWART H · 1995 to 2019
$9.9M
Structural studies of RNA processing and ubiquitin-like protein modificationR35GM118080 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI CHRISTOPHER D. LIMA · 2016 to 2026
$5.0M
STRUCTURAL STUDIES OF THE MRNA CAPPING APPARATUSR01GM061906 · NIGMS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI LIMA, CHRISTOPHER D. · 2000 to 2013
$4.8M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA008748NIGMS NIH HHS GM052470NIGMS NIH HHS GM061906NIGMS NIH HHS GM103403NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R01 GM052470NIGMS NIH HHS R01 GM061906NIGMS NIH HHS R35 GM118080
6 · The paper itself

Abstract

Protein phosphatases regulate mRNA synthesis and processing by remodeling the carboxy-terminal domain (CTD) of RNA polymerase II (Pol2) to dynamically inscribe a Pol2 CTD code. Fission yeast Fcp1 (SpFcp1) is an essential 723-amino acid CTD phosphatase that preferentially hydrolyzes Ser2-PO4 of the YS(2)PTSPS repeat. The SpFcp1 catalytic domain (aa 140-580) is composed of a DxDxT acyl-phosphatase module (FCPH) and a BRCT module. Here we conducted a genetic analysis of SpFcp1, which shows that (i) phosphatase catalytic activity is required for vegetative growth of fission yeast; (ii) the flanking amino-terminal domain (aa 1-139) and its putative metal-binding motif C(99)H(101)Cys(109)C(112) are essential; (iii) the carboxy-terminal domain (aa 581-723) is dispensable; (iv) a structurally disordered internal segment of the FCPH domain (aa 330-393) is dispensable; (v) lethal SpFcp1 mutations R271A and R299A are rescued by shortening the Pol2 CTD repeat array; and (vi) CTD Ser2-PO4 is not the only essential target of SpFcp1 in vivo. Recent studies highlight a second CTD code involving threonine phosphorylation of a repeat motif in transcription elongation factor Spt5. We find that Fcp1 can dephosphorylate Thr1-PO4 of the fission yeast Spt5 CTD nonamer repeat T(1)PAWNSGSK. We identify Arg271 as a governor of Pol2 versus Spt5 CTD substrate preference. Our findings implicate Fcp1 as a versatile sculptor of both the Pol2 and Spt5 CTD codes. Finally, we report a new 1.45 Å crystal structure of SpFcp1 with Mg(2+) and AlF3 that mimics an associative phosphorane transition state of the enzyme-aspartyl-phosphate hydrolysis reaction.

Indexed as

Amino Acid MotifsCatalytic DomainCrystallography, X-RayGenes, EssentialModels, MolecularMutationPhosphoprotein PhosphatasesPhosphorylationPhylogenyProtein Structure, SecondarySchizosaccharomycesSchizosaccharomyces pombe ProteinsSubstrate SpecificityTranscriptional Elongation FactorsFcp1 protein, S pombePhosphoprotein PhosphatasesSchizosaccharomyces pombe ProteinsSpt5 protein, S pombeTranscriptional Elongation FactorsCTD codeSpt5Ssu72

Identifiers

PMID25883047
PMCPMC4436666
OpenAlexW2134594820

What OpenQuestion holds

Textmetadata
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.