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Article: 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

TitleA 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
Authors
Issue Date2008
PublisherCold Spring Harbor Laboratory Press, Publications Department. The Journal's web site is located at http://www.genome.org
Citation
Genome Research, 2008, v. 18 n. 8, p. 1247-1258 How to Cite?
AbstractTo 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 ∼15% of alternative cassette exons are regulated by TIA1/TIAL1 via U-rich intronic elements. ©2008 by Cold Spring Harbor Laboratory Press.
Persistent Identifierhttp://hdl.handle.net/10722/138687
ISSN
2014 Impact Factor: 14.630
2014 SCImago Journal Rankings: 12.283
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorAznarez, Ien_HK
dc.contributor.authorBarash, Yen_HK
dc.contributor.authorShai, Oen_HK
dc.contributor.authorHe, Den_HK
dc.contributor.authorZielenski, Jen_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorParkinson, Jen_HK
dc.contributor.authorFrey, BJen_HK
dc.contributor.authorRommens, JMen_HK
dc.contributor.authorBlencowe, BJen_HK
dc.date.accessioned2011-09-07T02:21:38Z-
dc.date.available2011-09-07T02:21:38Z-
dc.date.issued2008en_HK
dc.identifier.citationGenome Research, 2008, v. 18 n. 8, p. 1247-1258en_HK
dc.identifier.issn1088-9051en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138687-
dc.description.abstractTo 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 ∼15% of alternative cassette exons are regulated by TIA1/TIAL1 via U-rich intronic elements. ©2008 by Cold Spring Harbor Laboratory Press.en_HK
dc.languageeng-
dc.publisherCold Spring Harbor Laboratory Press, Publications Department. The Journal's web site is located at http://www.genome.orgen_HK
dc.relation.ispartofGenome Researchen_HK
dc.subject.meshAlternative Splicing-
dc.subject.meshIntrons-
dc.subject.meshPoly(A)-Binding Proteins - antagonists and inhibitors - genetics - physiology-
dc.subject.meshRNA-Binding Proteins - antagonists and inhibitors - genetics - physiology-
dc.subject.meshRegulatory Sequences, Ribonucleic Acid-
dc.titleA 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 regulationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1088-9051&volume=18&issue=8&spage=1247&epage=1258&date=2008&atitle=A+systematic+analysis+of+intronic+sequences+downstream+of+5%27+splice+sites+reveals+a+widespread+role+for+U-rich+motifs+and+TIA1/TIAL1+proteins+in+alternative+splicing+regulation-
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1101/gr.073155.107en_HK
dc.identifier.pmid18456862-
dc.identifier.pmcidPMC2493427-
dc.identifier.scopuseid_2-s2.0-48949103996en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-48949103996&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1247en_HK
dc.identifier.epage1258en_HK
dc.identifier.isiWOS:000258116100006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridAznarez, I=6506570199en_HK
dc.identifier.scopusauthoridBarash, Y=7003653741en_HK
dc.identifier.scopusauthoridShai, O=6603601991en_HK
dc.identifier.scopusauthoridHe, D=36850269400en_HK
dc.identifier.scopusauthoridZielenski, J=7003732699en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridParkinson, J=18335998200en_HK
dc.identifier.scopusauthoridFrey, BJ=35459307900en_HK
dc.identifier.scopusauthoridRommens, JM=7006884140en_HK
dc.identifier.scopusauthoridBlencowe, BJ=7003332002en_HK
dc.identifier.citeulike6702616-

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