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Control of hnRNP A1 alternative splicing: an intron element represses use of the common 3' splice site.
Mol Cell Biol. 2000 Oct; 20(19):7353-62.MC

Abstract

Alternative splicing of exon 7B in the hnRNP A1 pre-mRNA produces mRNAs encoding two proteins: hnRNP A1 and the less abundant A1B. We have reported the identification of several intron elements that contribute to exon 7B skipping. In this study, we report the activity of a novel element, conserved element 9 (CE9), located in the intron downstream of exon 7B. We show that multiple copies of CE9 inhibit exon 7B-exon 8 splicing in vitro. When CE9 is inserted between two competing 3' splice sites, a single copy of CE9 decreases splicing to the distal 3' splice site. Our in vivo results also support the conclusion that CE9 is a splicing modulator. First, inserting multiple copies of CE9 into an A1 minigene compromises the production of fully spliced products. Second, one copy of CE9 stimulates the inclusion of a short internal exon in a derivative of the human beta-globin gene. In this case, in vitro splicing assays suggest that CE9 decreases splicing of intron 1, an event that improves splicing of intron 2 and decreases skipping of the short internal exon. The ability of CE9 to act on heterologous substrates, combined with the results of a competition assay, suggest that the activity of CE9 is mediated by a trans-acting factor. Our results indicate that CE9 represses the use of the common 3' splice site in the hnRNP A1 alternative splicing unit.

Authors+Show Affiliations

Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10982852

Citation

Simard, M J., and B Chabot. "Control of hnRNP A1 Alternative Splicing: an Intron Element Represses Use of the Common 3' Splice Site." Molecular and Cellular Biology, vol. 20, no. 19, 2000, pp. 7353-62.
Simard MJ, Chabot B. Control of hnRNP A1 alternative splicing: an intron element represses use of the common 3' splice site. Mol Cell Biol. 2000;20(19):7353-62.
Simard, M. J., & Chabot, B. (2000). Control of hnRNP A1 alternative splicing: an intron element represses use of the common 3' splice site. Molecular and Cellular Biology, 20(19), 7353-62.
Simard MJ, Chabot B. Control of hnRNP A1 Alternative Splicing: an Intron Element Represses Use of the Common 3' Splice Site. Mol Cell Biol. 2000;20(19):7353-62. PubMed PMID: 10982852.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Control of hnRNP A1 alternative splicing: an intron element represses use of the common 3' splice site. AU - Simard,M J, AU - Chabot,B, PY - 2000/9/13/pubmed PY - 2000/10/21/medline PY - 2000/9/13/entrez SP - 7353 EP - 62 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 20 IS - 19 N2 - Alternative splicing of exon 7B in the hnRNP A1 pre-mRNA produces mRNAs encoding two proteins: hnRNP A1 and the less abundant A1B. We have reported the identification of several intron elements that contribute to exon 7B skipping. In this study, we report the activity of a novel element, conserved element 9 (CE9), located in the intron downstream of exon 7B. We show that multiple copies of CE9 inhibit exon 7B-exon 8 splicing in vitro. When CE9 is inserted between two competing 3' splice sites, a single copy of CE9 decreases splicing to the distal 3' splice site. Our in vivo results also support the conclusion that CE9 is a splicing modulator. First, inserting multiple copies of CE9 into an A1 minigene compromises the production of fully spliced products. Second, one copy of CE9 stimulates the inclusion of a short internal exon in a derivative of the human beta-globin gene. In this case, in vitro splicing assays suggest that CE9 decreases splicing of intron 1, an event that improves splicing of intron 2 and decreases skipping of the short internal exon. The ability of CE9 to act on heterologous substrates, combined with the results of a competition assay, suggest that the activity of CE9 is mediated by a trans-acting factor. Our results indicate that CE9 represses the use of the common 3' splice site in the hnRNP A1 alternative splicing unit. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/10982852/Control_of_hnRNP_A1_alternative_splicing:_an_intron_element_represses_use_of_the_common_3'_splice_site_ L2 - https://journals.asm.org/doi/10.1128/mcb.20.19.7353-7362.2000?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -