The switch in alternative splicing of cyclic AMP-response element modulator protein CREM tau(2)alpha (activator) to CREM alpha (repressor) in human myometrial cells is mediated by SRp40

Tyson-Capper, A. J., Bailey, J., Krainer, A. R., Robson, S. C., Europe-Finner, G. N. (October 2005) The switch in alternative splicing of cyclic AMP-response element modulator protein CREM tau(2)alpha (activator) to CREM alpha (repressor) in human myometrial cells is mediated by SRp40. Journal of Biological Chemistry, 280 (41). pp. 34521-34529. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/16103121
DOI: 10.1074/jbc.M505344200

Abstract

The transcription factor cAMP-response element modulator (CREM) protein, plays a major role in cAMP-responsive gene regulation. Biological consequences resulting from the transcriptional stimuli of CREM are dictated by the expression of multiple protein isoforms generated by extensive alternative splicing of its precursor mRNA. We have previously shown that alternative splicing enables the expression of the CREM gene to be "switched" within the human myometrium during pregnancy from the production of CREM tau(2 alpha), a potent transcriptional activator to the synthesis of CREM alpha, a transcriptional repressor. Furthermore we have recently reported that this change in the expression of CREM spliced variants is likely to have important ramifications on the regulation of downstream cAMP-response element-responsive target genes involved in uterine activity during gestation. We have investigated the splicing factors involved in controlling the expression of myometrial CREM splice variants. Data presented here from transient transfections indicate that the switch in the synthesis of CREM tau(2)alpha to CREM alpha that occurs during pregnancy is regulated primarily by an SR protein family member, SRp40. We also show that expression of this splicing factor is tightly regulated in the myometrium during pregnancy. SRp40 regulates the splicing of CREM via its interactions with multiple ESE motifs present in the alternatively exons of CREM. In vitro splicing and electrophoretic mobility shift assays were employed to confirm the functionality of the SRp40-binding ESEs, thus providing a mechanistic explanation of how SRp40 regulates the switch in splicing from production of CREM tau(2)alpha to CREM alpha.

Item Type: Paper
Uncontrolled Keywords: SR proteins transcription factors in-vivo adenosine monophosphate adenosine_monophosphate binding protein preterm labor identification expression enhancer gene
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: CSHL Librarian
Date: October 2005
Date Deposited: 05 Jan 2012 15:59
Last Modified: 09 Apr 2014 15:42
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22724

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