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hnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly.
Mol Cell. 2013 Mar 07; 49(5):972-82.MC

Abstract

Pre-mRNA splicing is catalyzed through the activity of the spliceosome, a dynamic enzymatic complex. Forcing aberrant interactions within the spliceosome can reduce splicing efficiency and alter splice site choice; however, it is unknown whether such alterations are naturally exploited mechanisms of splicing regulation. Here, we demonstrate that hnRNP L represses CD45 exon 4 by recruiting hnRNP A1 to a sequence upstream of the 5' splice site. Together, hnRNP L and A1 induce extended contacts between the 5' splice site-bound U1 snRNA and neighboring exonic sequences that, in turn, inhibit stable association of U6 snRNA and subsequent catalysis. Importantly, analysis of several exons regulated by hnRNP L shows a clear relationship between the potential for binding of hnRNP A1 and U1 snRNA and the effect of hnRNP L on splicing. Together, our results demonstrate that conformational perturbations within the spliceosome are a naturally occurring and generalizable mechanism for controlling alternative splicing decisions.

Authors+Show Affiliations

Department of Biochemistry and Biophysics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104-6059, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23394998

Citation

Chiou, Ni-Ting, et al. "HnRNP L and hnRNP A1 Induce Extended U1 snRNA Interactions With an Exon to Repress Spliceosome Assembly." Molecular Cell, vol. 49, no. 5, 2013, pp. 972-82.
Chiou NT, Shankarling G, Lynch KW. HnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly. Mol Cell. 2013;49(5):972-82.
Chiou, N. T., Shankarling, G., & Lynch, K. W. (2013). HnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly. Molecular Cell, 49(5), 972-82. https://doi.org/10.1016/j.molcel.2012.12.025
Chiou NT, Shankarling G, Lynch KW. HnRNP L and hnRNP A1 Induce Extended U1 snRNA Interactions With an Exon to Repress Spliceosome Assembly. Mol Cell. 2013 Mar 7;49(5):972-82. PubMed PMID: 23394998.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - hnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly. AU - Chiou,Ni-Ting, AU - Shankarling,Ganesh, AU - Lynch,Kristen W, Y1 - 2013/02/07/ PY - 2012/07/30/received PY - 2012/11/16/revised PY - 2012/12/20/accepted PY - 2013/2/12/entrez PY - 2013/2/12/pubmed PY - 2013/5/1/medline SP - 972 EP - 82 JF - Molecular cell JO - Mol Cell VL - 49 IS - 5 N2 - Pre-mRNA splicing is catalyzed through the activity of the spliceosome, a dynamic enzymatic complex. Forcing aberrant interactions within the spliceosome can reduce splicing efficiency and alter splice site choice; however, it is unknown whether such alterations are naturally exploited mechanisms of splicing regulation. Here, we demonstrate that hnRNP L represses CD45 exon 4 by recruiting hnRNP A1 to a sequence upstream of the 5' splice site. Together, hnRNP L and A1 induce extended contacts between the 5' splice site-bound U1 snRNA and neighboring exonic sequences that, in turn, inhibit stable association of U6 snRNA and subsequent catalysis. Importantly, analysis of several exons regulated by hnRNP L shows a clear relationship between the potential for binding of hnRNP A1 and U1 snRNA and the effect of hnRNP L on splicing. Together, our results demonstrate that conformational perturbations within the spliceosome are a naturally occurring and generalizable mechanism for controlling alternative splicing decisions. SN - 1097-4164 UR - https://www.unboundmedicine.com/medline/citation/23394998/hnRNP_L_and_hnRNP_A1_induce_extended_U1_snRNA_interactions_with_an_exon_to_repress_spliceosome_assembly_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1097-2765(13)00038-5 DB - PRIME DP - Unbound Medicine ER -