Evidence map›Paper›PMID 38268025›Full record

ArticleGenome biology2024

The unusual gene architecture of polyubiquitin is created by dual-specific splice sites.

Chaorui Duan, Truman Mooney, Luke Buerer, Cory Bowers, Stephen Rong, Seong Won Kim, Alger M Fredericks, Sean F Monaghan, William G Fairbrother

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Detection of a sequence feature for recursive splicing.bioRxiv : the preprint server for biology · 2026
    Article
  2. 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

9 authors at 2 institutions in 1 country.

Chaorui DuanDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02903, USA.
Truman MooneyDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02903, USA.
Luke BuererDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02903, USA.
Cory BowersDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02903, USA.
Stephen RongDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02903, USA.
Seong Won KimDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02903, USA.
Alger M FredericksDepartment of Surgery, The Miriam Hospital, Providence, RI, 02906, USA.
Sean F MonaghanDivision of Surgical Research, Department of Surgery, Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI, 02903, USA.
William G FairbrotherDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02903, USA. william_fairbrother@brown.edu.
Brown University · USMiriam Hospital · US

Funding

Uncoupling of IL-1 beta and VEGF-A Crosstalk Contributes to Impaired Arteriogenesis Response to Ischemia in Chronic Diabetes MellitusP20GM103652 · NIGMS · OCEAN STATE RESEARCH INSTITUTE, INC. · PI CHOUDHARY, GAURAV, HARRINGTON, ELIZABETH O · 2013 to 2022
$21.3M
Using Genomic Epidemiology to Identify Transmission Patterns and Inform Intervention Strategies for Antibiotic-Resistant N. GonorrhoeaeP20GM121344 · NIGMS · MIRIAM HOSPITAL · PI D'AGATA, ERIKA M · 2018 to 2022
$9.4M
Discovering Splicing Defects in Human GenesR01GM127472 · NIGMS · BROWN UNIVERSITY · PI William G Fairbrother · 2018 to 2026
$5.9M
A genomic approach to studying the life cycle of intron lariatsR01GM105681 · NIGMS · BROWN UNIVERSITY · PI FAIRBROTHER, WILLIAM G · 2014 to 2022
$3.7M
Improving Sepsis Care with Deep RNA Sequencing DataR35GM142638 · NIGMS · RHODE ISLAND HOSPITAL · PI Sean Farrell Monaghan · 2021 to 2026
$2.6M
Short-Term Training Program to Increase Diversity in Health-Related ResearchR25HL088992 · NHLBI · BROWN UNIVERSITY · PI ABID, RUHUL, DIAZ, JOSEPH A · 2007 to 2024
$1.9M
NHLBI NIH HHS R25 HL088992NIGMS NIH HHS P20 GM103652NIGMS NIH HHS P20 GM121344NIGMS NIH HHS R01 GM105681NIGMS NIH HHS R01 GM127472NIGMS NIH HHS R35 GM142638NIH HHS P20 GM121344NIH HHS R35 GM142638
6 · The paper itself

Abstract

backgroundThe removal of introns occurs through the splicing of a 5' splice site (5'ss) with a 3' splice site (3'ss). These two elements are recognized by distinct components of the spliceosome. However, introns in higher eukaryotes contain many matches to the 5' and 3' splice-site motifs that are presumed not to be used.

resultsHere, we find that many of these sites can be used. We also find occurrences of the AGGT motif that can function as either a 5'ss or a 3'ss-previously referred to as dual-specific splice sites (DSSs)-within introns. Analysis of the Sequence Read Archive reveals a 3.1-fold enrichment of DSSs relative to expectation, implying synergy between the ability to function as a 5'ss and 3'ss. Despite this suggested mechanistic advantage, DSSs are 2.7- and 4.7-fold underrepresented in annotated 5' and 3' splice sites. A curious exception is the polyubiquitin gene UBC, which contains a tandem array of DSSs that precisely delimit the boundary of each ubiquitin monomer. The resulting isoforms splice stochastically to include a variable number of ubiquitin monomers. We found no evidence of tissue-specific or feedback regulation but note the 8.4-fold enrichment of DSS-spliced introns in tandem repeat genes suggests a driving role in the evolution of genes like UBC.

conclusionsWe find an excess of unannotated splice sites and the utilization of DSSs in tandem repeats supports the role of splicing in gene evolution. These findings enhance our understanding of the diverse and complex nature of the splicing process.

Indexed as

PolyubiquitinRNA SplicingArchivesIntronsRNA Splice SitesPolyubiquitinRNA Splice SitesDual-specific splice sitesRNA splicingSynergyUBC

Identifiers

PMID38268025
PMCPMC10809524
OpenAlexW4391160600

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.