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Antagonistic effects of the SRp30c protein and cryptic 5' splice sites on the alternative splicing of the apoptotic regulator Bcl-x.
J Biol Chem. 2008 Aug 01; 283(31):21315-24.JB

Abstract

Alternative 5' splice site selection allows Bcl-x to produce two isoforms with opposite effects on apoptosis. The pro-apoptotic Bcl-x(S) variant is up-regulated by ceramide and down-regulated by protein kinase C through specific cis-acting exonic elements, one of which is bound by SAP155. Splicing to the Bcl-x(S) 5' splice site is also enforced by heterogeneous nuclear ribonucleoprotein (hnRNP) F/H proteins and by Sam68 in cooperation with hnRNP A1. Here, we have characterized exon elements that influence splicing to the 5' splice site of the anti-apoptotic Bcl-x(L) isoform. Within a 86-nucleotide region (B3) located immediately upstream of the Bcl-x(L) donor site we have identified two elements (ML2 and AM2) that stimulate splicing to the Bcl-x(L) 5' splice site. SRp30c binds to these elements and can shift splicing to the 5' splice site of Bcl-x(L) in an ML2/AM2-dependent manner in vitro and in vivo. The B3 region also contains an element that represses the use of Bcl-x(L). This element is bound by U1 small nuclear ribonucleoprotein and contains two 5' splice sites that can be used when the Bcl-x(L) 5' splice site is mutated or the ML2/AM2 elements are deleted. Conversely, mutating the cryptic 5' splice sites stimulates splicing to the Bcl-x(L) site. Thus, SRp30c stimulates splicing to the downstream 5' splice site of Bcl-x(L), thereby attenuating the repressive effect of upstream U1 snRNP binding sites.

Authors+Show Affiliations

RNA/RNP Group, Département de Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18534987

Citation

Cloutier, Philippe, et al. "Antagonistic Effects of the SRp30c Protein and Cryptic 5' Splice Sites On the Alternative Splicing of the Apoptotic Regulator Bcl-x." The Journal of Biological Chemistry, vol. 283, no. 31, 2008, pp. 21315-24.
Cloutier P, Toutant J, Shkreta L, et al. Antagonistic effects of the SRp30c protein and cryptic 5' splice sites on the alternative splicing of the apoptotic regulator Bcl-x. J Biol Chem. 2008;283(31):21315-24.
Cloutier, P., Toutant, J., Shkreta, L., Goekjian, S., Revil, T., & Chabot, B. (2008). Antagonistic effects of the SRp30c protein and cryptic 5' splice sites on the alternative splicing of the apoptotic regulator Bcl-x. The Journal of Biological Chemistry, 283(31), 21315-24. https://doi.org/10.1074/jbc.M800353200
Cloutier P, et al. Antagonistic Effects of the SRp30c Protein and Cryptic 5' Splice Sites On the Alternative Splicing of the Apoptotic Regulator Bcl-x. J Biol Chem. 2008 Aug 1;283(31):21315-24. PubMed PMID: 18534987.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antagonistic effects of the SRp30c protein and cryptic 5' splice sites on the alternative splicing of the apoptotic regulator Bcl-x. AU - Cloutier,Philippe, AU - Toutant,Johanne, AU - Shkreta,Lulzim, AU - Goekjian,Serge, AU - Revil,Timothée, AU - Chabot,Benoit, Y1 - 2008/06/05/ PY - 2008/6/7/pubmed PY - 2008/9/23/medline PY - 2008/6/7/entrez SP - 21315 EP - 24 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 283 IS - 31 N2 - Alternative 5' splice site selection allows Bcl-x to produce two isoforms with opposite effects on apoptosis. The pro-apoptotic Bcl-x(S) variant is up-regulated by ceramide and down-regulated by protein kinase C through specific cis-acting exonic elements, one of which is bound by SAP155. Splicing to the Bcl-x(S) 5' splice site is also enforced by heterogeneous nuclear ribonucleoprotein (hnRNP) F/H proteins and by Sam68 in cooperation with hnRNP A1. Here, we have characterized exon elements that influence splicing to the 5' splice site of the anti-apoptotic Bcl-x(L) isoform. Within a 86-nucleotide region (B3) located immediately upstream of the Bcl-x(L) donor site we have identified two elements (ML2 and AM2) that stimulate splicing to the Bcl-x(L) 5' splice site. SRp30c binds to these elements and can shift splicing to the 5' splice site of Bcl-x(L) in an ML2/AM2-dependent manner in vitro and in vivo. The B3 region also contains an element that represses the use of Bcl-x(L). This element is bound by U1 small nuclear ribonucleoprotein and contains two 5' splice sites that can be used when the Bcl-x(L) 5' splice site is mutated or the ML2/AM2 elements are deleted. Conversely, mutating the cryptic 5' splice sites stimulates splicing to the Bcl-x(L) site. Thus, SRp30c stimulates splicing to the downstream 5' splice site of Bcl-x(L), thereby attenuating the repressive effect of upstream U1 snRNP binding sites. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/18534987/Antagonistic_effects_of_the_SRp30c_protein_and_cryptic_5'_splice_sites_on_the_alternative_splicing_of_the_apoptotic_regulator_Bcl_x_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=18534987 DB - PRIME DP - Unbound Medicine ER -