Evidence map›Paper›PMID 31600193›Full record

ArticlePLoS biology2019

Spliceosomal Prp8 intein at the crossroads of protein and RNA splicing.

Cathleen M Green, Zhong Li, Aaron D Smith, Olga Novikova, Valjean R Bacot-Davis, Fengshan Gao, Saiyang Hu, Nilesh K Banavali, Dennis J Thiele, Hongmin Li and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

27 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. A Unique THN Motif Is Critical for Enabling Efficient C-Terminal Traceless Cleavage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Massive intein content inProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  12. Article
  13. Article
  14. Review
  15. Calcimycin InhibitsACS infectious diseases · 2022
    Article
  16. Journal of fungi (Basel, Switzerland) · 2022
    Article
  17. Article
  18. Review
  19. Inteins as Drug Targets and Therapeutic Tools.Frontiers in molecular biosciences · 2022
    Review
  20. 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

11 authors at 3 institutions in 1 country.

Cathleen M GreenDepartment of Biological Sciences and RNA Institute, University at Albany, Albany, New York, United States of America.
Zhong LiDivision of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
Aaron D SmithDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Olga NovikovaDepartment of Biological Sciences and RNA Institute, University at Albany, Albany, New York, United States of America.
Valjean R Bacot-DavisDepartment of Biological Sciences and RNA Institute, University at Albany, Albany, New York, United States of America.ORCID 0000-0001-6620-6560
Fengshan GaoDivision of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.ORCID 0000-0003-1646-5227
Saiyang HuDivision of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
Nilesh K BanavaliDivision of Translational Medicine, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.ORCID 0000-0003-2206-7049
Dennis J ThieleDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Hongmin LiDivision of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.ORCID 0000-0002-8684-5308
Marlene BelfortDepartment of Biological Sciences and RNA Institute, University at Albany, Albany, New York, United States of America.ORCID 0000-0002-1592-5618
New York State Department of Health · USUniversity at Albany, State University of New York · USDuke University · US

Funding

X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
SELF-SPLICING INTEINS: FUNCTION, EVOLUTION, APPLICATIONR01GM044844 · NIGMS · WADSWORTH CENTER · PI BELFORT, MARLENE · 1990 to 2019
$8.9M
Tri-Institutional Molecular Mycology and Pathogenesis Training ProgramT32AI052080 · NIAID · DUKE UNIVERSITY · PI ANDREW ALSPAUGH, JOSEPH HEITMAN · 2003 to 2026
$8.7M
Metal Homeostasis in YeastR01GM041840 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALSPAUGH, ANDREW · 1989 to 2022
$6.5M
SELF-SPLICING INTRONS IN THE PHAGE T4/E COLI SYSTEMR01GM039422 · NIGMS · WADSWORTH CENTER · PI BELFORT, MARLENE · 1988 to 2019
$5.3M
INTRON DYNAMICS IN BACTERIAR37GM039422 · NIGMS · WADSWORTH CENTER · PI BELFORT, MARLENE · 2001 to 2010
$4.0M
High throughput screening of the Prp8 intein splicing inhibitors for pathogenic fungiR01AI140726 · NIAID · WADSWORTH CENTER · PI LI, HONGMIN · 2019 to 2022
$2.4M
Discovery of therapeutics against Cryptococcosis by Repurposing Pharmaceutical LibrariesR21AI141178 · NIAID · WADSWORTH CENTER · PI LI, HONGMIN · 2019 to 2020
$441k
NIAID NIH HHS R01 AI140726NIAID NIH HHS R21 AI141178NIAID NIH HHS T32 AI052080NIGMS NIH HHS P41 GM103393NIGMS NIH HHS R01 GM039422NIGMS NIH HHS R01 GM041840NIGMS NIH HHS R01 GM044844NIGMS NIH HHS R37 GM039422
6 · The paper itself

Abstract

The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNAs. At its functional core lies the essential pre-mRNA processing factor 8 (Prp8) protein. Across diverse eukaryotes, this protein cofactor of RNA catalysis harbors a self-splicing element called an intein. Inteins in Prp8 are extremely pervasive and are found at 7 different sites in various species. Here, we focus on the Prp8 intein from Cryptococcus neoformans (Cne), a human fungal pathogen. We solved the crystal structure of this intein, revealing structural homology among protein splicing sequences in eukaryotes, including the Hedgehog C terminus. Working with the Cne Prp8 intein in a reporter assay, we find that the biologically relevant divalent metals copper and zinc inhibit intein splicing, albeit by 2 different mechanisms. Copper likely stimulates reversible modifications on a catalytically important cysteine, whereas zinc binds at the terminal asparagine and the same critical cysteine. Importantly, we also show that copper treatment inhibits Prp8 protein splicing in Cne. Lastly, an intein-containing Prp8 precursor model is presented, suggesting that metal-induced protein splicing inhibition would disturb function of both Prp8 and the spliceosome. These results indicate that Prp8 protein splicing can be modulated, with potential functional implications for the spliceosome.

Indexed as

RNA SplicingAsparagineBinding SitesCloning, MolecularCopperCryptococcus neoformansCrystallography, X-RayCysteineEscherichia coliFungal ProteinsGene ExpressionGenes, ReporterGenetic VectorsGreen Fluorescent ProteinsInteinsMaltose-Binding ProteinsAsparagineCopperCysteineFungal ProteinsGreen Fluorescent ProteinsMaltose-Binding ProteinsRecombinant Fusion ProteinsRNA-Binding ProteinsZinc

Identifiers

PMID31600193
PMCPMC6805012
OpenAlexW2979812786

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.