Evidence map›Paper›PMID 25670679›Full record

ArticleNucleic acids research2015

Brr2 plays a role in spliceosomal activation in addition to U4/U6 unwinding.

Lingdi Zhang, Xueni Li, Ryan C Hill, Yan Qiu, Wenzheng Zhang, Kirk C Hansen, Rui Zhao

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-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

18 citing papers in PubMed, 29 citations in OpenAlex.

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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

7 authors at 2 institutions in 2 countries.

Lingdi ZhangDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Xueni LiDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Ryan C HillDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Yan QiuCollege of Bioscience and Bioengineering, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China.
Wenzheng ZhangDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Kirk C HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Rui ZhaoDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA rui.zhao@ucdenver.edu.
University of Colorado Denver · USBioscience (China) · CN

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Understanding the structure and function of splicing factor Prp8R01GM080334 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ZHAO, RUI · 2008 to 2012
$1.5M
LTQ FT-ICR Hybrid Mass Spectrometer PurchaseS10RR023015 · NCRR · UNIVERSITY OF COLORADO DENVER · PI HANSEN, KIRK C · 2007 to 2007
$1.1M
Spinal muscular atrophy therapy using recombinant SMN proteinsR21NS085514 · NINDS · UNIVERSITY OF COLORADO DENVER · PI ZHAO, RUI · 2014 to 2015
$427k
NCATS NIH HHS UL1 TR001082NCRR NIH HHS S10RR023015NIGMS NIH HHS R01GM080334NINDS NIH HHS R21NS085514
6 · The paper itself

Abstract

Brr2 is a DExD/H-box RNA helicase that is responsible for U4/U6 unwinding, a critical step in spliceosomal activation. Brr2 is a large protein (∼250 kD) that consists of an N-terminal domain (∼500 residues) with unknown function and two Hel308-like modules that are responsible for RNA unwinding. Here we demonstrate that removal of the entire N-terminal domain is lethal to Saccharomyces cerevisiae and deletion of the N-terminal 120 residues leads to splicing defects and severely impaired growth. This N-terminal truncation does not significantly affect Brr2's helicase activity. Brr2-Δ120 can be successfully assembled into the tri-snRNP (albeit at a lower level than the WT Brr2) and the spliceosomal B complex. However, the truncation significantly impairs spliceosomal activation, leading to a dramatic reduction of U5, U6 snRNAs and accumulation of U1 snRNA in the B(act) complex. The N-terminal domain of Brr2 does not seem to be directly involved in regulating U1/5'ss unwinding. Instead, the N-terminal domain seems to be critical for retaining U5 and U6 snRNPs during/after spliceosomal activation through its interaction with snRNAs and possibly other spliceosomal proteins, revealing a new role of Brr2 in spliceosomal activation in addition to U4/U6 unwinding.

Indexed as

Genes, FungalPeptide FragmentsProtein Structure, TertiaryRibonucleoprotein, U4-U6 Small NuclearRNA, FungalRNA HelicasesRNA PrecursorsRNA, Small NuclearRNA SplicingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSpliceosomesBRR2 protein, S cerevisiaePeptide FragmentsRibonucleoprotein, U4-U6 Small NuclearRNA, FungalRNA HelicasesRNA PrecursorsRNA, Small NuclearSaccharomyces cerevisiae Proteins

Identifiers

PMID25670679
PMCPMC4381053
OpenAlexW2112016696

What OpenQuestion holds

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LicenceCC BY
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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.