Evidence map›Paper›PMID 18456862›Full record

ArticleGenome research2008

A systematic analysis of intronic sequences downstream of 5' splice sites reveals a widespread role for U-rich motifs and TIA1/TIAL1 proteins in alternative splicing regulation.

Isabel Aznarez, Yoseph Barash, Ofer Shai, David He, Julian Zielenski, Lap-Chee Tsui, John Parkinson, Brendan J Frey, Johanna M Rommens, Benjamin J Blencowe

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing 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.

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3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 100 citations in OpenAlex.

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  12. T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology.International journal of molecular sciences · 2022
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10 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

10 authors at 3 institutions in 3 countries.

Isabel AznarezProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Yoseph Barash
Ofer Shai
David He
Julian Zielenski
Lap-Chee Tsui
John Parkinson
Brendan J Frey
Johanna M Rommens
Benjamin J Blencowe
University of Toronto · CAHospital for Sick Children · CAUniversity of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To identify human intronic sequences associated with 5' splice site recognition, we performed a systematic search for motifs enriched in introns downstream of both constitutive and alternative cassette exons. Significant enrichment was observed for U-rich motifs within 100 nucleotides downstream of 5' splice sites of both classes of exons, with the highest enrichment between positions +6 and +30. Exons adjacent to U-rich intronic motifs contain lower frequencies of exonic splicing enhancers and higher frequencies of exonic splicing silencers, compared with exons not followed by U-rich intronic motifs. These findings motivated us to explore the possibility of a widespread role for U-rich motifs in promoting exon inclusion. Since cytotoxic granule-associated RNA binding protein (TIA1) and TIA1-like 1 (TIAL1; also known as TIAR) were previously shown in vitro to bind to U-rich motifs downstream of 5' splice sites, and to facilitate 5' splice site recognition in vitro and in vivo, we investigated whether these factors function more generally in the regulation of splicing of exons followed by U-rich intronic motifs. Simultaneous knockdown of TIA1 and TIAL1 resulted in increased skipping of 36/41 (88%) of alternatively spliced exons associated with U-rich motifs, but did not affect 32/33 (97%) alternatively spliced exons that are not associated with U-rich motifs. The increase in exon skipping correlated with the proximity of the first U-rich motif and the overall "U-richness" of the adjacent intronic region. The majority of the alternative splicing events regulated by TIA1/TIAL1 are conserved in mouse, and the corresponding genes are associated with diverse cellular functions. Based on our results, we estimate that approximately 15% of alternative cassette exons are regulated by TIA1/TIAL1 via U-rich intronic elements.

Indexed as

Alternative SplicingIntronsRegulatory Sequences, Ribonucleic AcidRNA Splice SitesAnimalsExonsHeLa CellsHumansMicePoly(A)-Binding ProteinsRNA-Binding ProteinsRNA InterferenceSequence Analysis, RNAT-Cell Intracellular Antigen-1UridinePoly(A)-Binding ProteinsRegulatory Sequences, Ribonucleic AcidRNA-Binding ProteinsRNA Splice SitesT-Cell Intracellular Antigen-1TIA1 protein, humanTIAL1 protein, humanUridine

Identifiers

PMID18456862
PMCPMC2493427
OpenAlexW2170702502

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.