Evidence map›Paper›PMID 23376934›Full record

ArticleNucleic acids research2013

U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs.

Jermaine L Jenkins, Anant A Agrawal, Ankit Gupta, Michael R Green, Clara L Kielkopf

Abstract read
In one paragraph

Article in Nucleic acids research, 2013. 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
–field-weighted citation impact
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.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Early Splicing Complexes and Human Disease.International journal of molecular sciences · 2023
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
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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

5 authors.

Jermaine L JenkinsCenter for RNA Biology and Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Anant A Agrawal
Ankit Gupta
Michael R Green
Clara L Kielkopf

Funding

ZWITTERION SURFACTANT DDMAB FOR IMPROV STABIL OF PROTEINP41RR001209 · NCRR · STANFORD UNIVERSITY · PI GONZALEZ, ANA M · 1985 to 2011
$38.9M
Overall (pp. 40-62)P41GM103485 · NIGMS · CORNELL UNIVERSITY · PI CERIONE, RICHARD A. · 2012 to 2018
$15.5M
Virology/Immunology CoreP30AI078498 · NIAID · UNIVERSITY OF ROCHESTER · PI DEWHURST, STEPHEN · 2008 to 2018
$14.6M
Molecular Recognition During Pre-mRNA SplicingR01GM070503 · NIGMS · UNIVERSITY OF ROCHESTER · PI KIELKOPF, CLARA · 2004 to 2025
$7.9M
SPLICING OF MRNA PRECURSORSR01GM035490 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GREEN, MICHAEL R · 1985 to 2021
$4.7M
A shared macromolecular X-ray diffraction system in RochesterS10RR026501 · NCRR · UNIVERSITY OF ROCHESTER · PI WEDEKIND, JOSEPH E · 2010 to 2010
$478k
BIAcore T100 for research and drug discovery in RochesterS10RR027241 · NCRR · UNIVERSITY OF ROCHESTER · PI KIELKOPF, CLARA · 2010 to 2010
$365k
NCRR NIH HHS 1S10 RR026501NCRR NIH HHS 1S10 RR027241NCRR NIH HHS P41RR001209NIAID NIH HHS P30 AI078498NIGMS NIH HHS GM103485NIGMS NIH HHS R01 GM035490NIGMS NIH HHS R01 GM070503
6 · The paper itself

Abstract

Degenerate splice site sequences mark the intron boundaries of pre-mRNA transcripts in multicellular eukaryotes. The essential pre-mRNA splicing factor U2AF(65) is faced with the paradoxical tasks of accurately targeting polypyrimidine (Py) tracts preceding 3' splice sites while adapting to both cytidine and uridine nucleotides with nearly equivalent frequencies. To understand how U2AF(65) recognizes degenerate Py tracts, we determined six crystal structures of human U2AF(65) bound to cytidine-containing Py tracts. As deoxy-ribose backbones were required for co-crystallization with these Py tracts, we also determined two baseline structures of U2AF(65) bound to the deoxy-uridine counterparts and compared the original, RNA-bound structure. Local structural changes suggest that the N-terminal RNA recognition motif 1 (RRM1) is more promiscuous for cytosine-containing Py tracts than the C-terminal RRM2. These structural differences between the RRMs were reinforced by the specificities of wild-type and site-directed mutant U2AF(65) for region-dependent cytosine- and uracil-containing RNA sites. Small-angle X-ray scattering analyses further demonstrated that Py tract variations select distinct inter-RRM spacings from a pre-existing ensemble of U2AF(65) conformations. Our results highlight both local and global conformational selection as a means for universal 3' splice site recognition by U2AF(65).

Indexed as

RNA Splice SitesAmino Acid MotifsCytidineHumansModels, MolecularNuclear ProteinsProtein BindingPyrimidinesRibonucleoproteinsRNA, MessengerRNA PrecursorsSplicing Factor U2AFUridineCytidineNuclear ProteinsPyrimidinesRibonucleoproteinsRNA, MessengerRNA PrecursorsRNA Splice SitesSplicing Factor U2AFU2AF2 protein, humanUridine

Identifiers

PMID23376934
PMCPMC3616741

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Registered trials

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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.