Evidence map›Paper›PMID 18719244›Full record

ArticleRNA (New York, N.Y.)2008

A cell-based screen for splicing regulators identifies hnRNP LL as a distinct signal-induced repressor of CD45 variable exon 4.

Justin D Topp, Jason Jackson, Alexis A Melton, Kristen W Lynch

Open access · bronzeAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% 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

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Regulation of CD45 isoforms during human effector and memory CD8 T cell differentiation: Implications for T cell nomenclature.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  19. Review
  20. SpliceRCA:ACS central science · 2018
    Article

12 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Justin D ToppDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038, USA.
Jason Jackson
Alexis A Melton
Kristen W Lynch
The University of Texas Southwestern Medical Center · US

Funding

Mechanisms of Signal-Induced Alternative Splicing: CD45R01GM067719 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI LYNCH, KRISTEN W · 2003 to 2015
$3.8M
Identification of signal-induced splicing regulatorsF32GM083620 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI TOPP, JUSTIN D · 2007 to 2007
$50k
NIGMS NIH HHS F32 GM083620NIGMS NIH HHS R01 GM067719
6 · The paper itself

Abstract

The human CD45 gene encodes a protein-tyrosine phosphatase that exhibits differential isoform expression in resting and activated T cells due to alternative splicing of three variable exons. Previously, we have used biochemical methods to identify two regulatory proteins, hnRNP L and PSF, which contribute to the activation-induced skipping of CD45 via the ESS1 regulatory element in variable exon 4. Here we report the identification of a third CD45 regulatory factor, hnRNP L-like (hnRNP LL), via a cell-based screen for clonal variants that exhibit an activation-like phenotype of CD45 splicing even under resting conditions. Microarray analysis of two splicing-altered clones revealed increased expression of hnRNP LL relative to wild-type cells. We further demonstrate that both the expression of hnRNP LL protein and its binding to ESS1 are up-regulated in wild-type cells upon activation. Forced overexpression of hnRNP LL in wild-type cells results in an increase in exon repression, while knock-down of hnRNP LL eliminates activation-induced exon skipping. Interestingly, analysis of the binding of hnRNP L and hnRNP LL to mutants of ESS1 reveals that these proteins have overlapping, but distinct binding requirements. Together, these data establish that hnRNP LL plays a critical and unique role in the signal-induced regulation of CD45 and demonstrate the utility of cell-based screens for the identification of novel splicing regulatory factors.

Indexed as

Gene Expression Regulation, EnzymologicRNA SplicingExonsGenes, ReporterGenetic VariationHeterogeneous-Nuclear RibonucleoproteinsHumansLeukocyte Common AntigensLymphocyte ActivationMutationOligonucleotide Array Sequence AnalysisRegulatory Elements, TranscriptionalRepressor ProteinsT-LymphocytesUp-RegulationHeterogeneous-Nuclear RibonucleoproteinsHNRNPLL protein, humanLeukocyte Common AntigensRepressor Proteins

Identifiers

PMID18719244
PMCPMC2553740
OpenAlexW2114212941

What OpenQuestion holds

Textmetadata
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.