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Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization.
EMBO J. 1999 Apr 01; 18(7):1939-52.EJ

Abstract

The RNA-binding protein hnRNP A1 is a splicing regulator produced by exclusion of alternative exon 7B from the A1 pre-mRNA. Each intron flanking exon 7B contains a high-affinity A1-binding site. The A1-binding elements promote exon skipping in vivo, activate distal 5' splice site selection in vitro and improve the responsiveness of pre-mRNAs to increases in the concentration of A1. Whereas the glycine-rich C-terminal domain of A1 is not required for binding, it is essential to activate the distal 5' splice site. Because A1 complexes can interact simultaneously with two A1-binding sites, we propose that an interaction between bound A1 proteins facilitates the pairing of distant splice sites. Based on the distribution of putative A1-binding sites in various pre-mRNAs, an A1-mediated change in pre-mRNA conformation may help define the borders of mammalian introns. We also identify an intron element which represses the 3' splice site of exon 7B. The activity of this element is mediated by a factor distinct from A1. Our results suggest that exon 7B skipping results from the concerted action of several intron elements that modulate splice site recognition and pairing.

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

10202157

Citation

Blanchette, M, and B Chabot. "Modulation of Exon Skipping By High-affinity hnRNP A1-binding Sites and By Intron Elements That Repress Splice Site Utilization." The EMBO Journal, vol. 18, no. 7, 1999, pp. 1939-52.
Blanchette M, Chabot B. Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization. EMBO J. 1999;18(7):1939-52.
Blanchette, M., & Chabot, B. (1999). Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization. The EMBO Journal, 18(7), 1939-52.
Blanchette M, Chabot B. Modulation of Exon Skipping By High-affinity hnRNP A1-binding Sites and By Intron Elements That Repress Splice Site Utilization. EMBO J. 1999 Apr 1;18(7):1939-52. PubMed PMID: 10202157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization. AU - Blanchette,M, AU - Chabot,B, PY - 1999/4/15/pubmed PY - 1999/4/15/medline PY - 1999/4/15/entrez SP - 1939 EP - 52 JF - The EMBO journal JO - EMBO J. VL - 18 IS - 7 N2 - The RNA-binding protein hnRNP A1 is a splicing regulator produced by exclusion of alternative exon 7B from the A1 pre-mRNA. Each intron flanking exon 7B contains a high-affinity A1-binding site. The A1-binding elements promote exon skipping in vivo, activate distal 5' splice site selection in vitro and improve the responsiveness of pre-mRNAs to increases in the concentration of A1. Whereas the glycine-rich C-terminal domain of A1 is not required for binding, it is essential to activate the distal 5' splice site. Because A1 complexes can interact simultaneously with two A1-binding sites, we propose that an interaction between bound A1 proteins facilitates the pairing of distant splice sites. Based on the distribution of putative A1-binding sites in various pre-mRNAs, an A1-mediated change in pre-mRNA conformation may help define the borders of mammalian introns. We also identify an intron element which represses the 3' splice site of exon 7B. The activity of this element is mediated by a factor distinct from A1. Our results suggest that exon 7B skipping results from the concerted action of several intron elements that modulate splice site recognition and pairing. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/10202157/Modulation_of_exon_skipping_by_high_affinity_hnRNP_A1_binding_sites_and_by_intron_elements_that_repress_splice_site_utilization_ L2 - https://doi.org/10.1093/emboj/18.7.1939 DB - PRIME DP - Unbound Medicine ER -