Title

Investigation of connexin 43 expression in response to estrogen and discovery of novel promoters and exons in the connexin 43 gene

Date of Award

2004

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Biochemistry and Molecular Biology

First Committee Member

Rudolf Werner, Committee Chair

Abstract

Connexin 43 (Cx43) is the major gap junction protein in the term uterine muscle. Its expression appears to be induced by estrogen at parturition, when coordinated contraction of the uterine smooth muscle is required for the expulsion of the fetus. The present study identifies an estrogen responsive element located in the Cx43 5' UTR. This element seems to regulate Cx43 expression at the translational level, and furthermore, it requires the presence of the Cx43 promoter to function in the estrogen response of the gene.The Cx43 gene was originally described as consisting of two exons, one coding for most of the 5' UTR, and the other for the protein sequence and 3' UTR. In this study, it is reported that in mouse, four additional exons are expressed, all coding for novel 5 ' UTRs. Altogether eight novel Cx43 mRNA species (Genbank accession numbers AY427554 to AY427561), generated by differential promoter usage and alternative splicing mechanisms, were identified. The relative abundance of these mRNAs varied in a tissue-specific manner. In addition, the alternative transcripts displayed different translational efficiencies in several cell lines, indicating the presence of cis-acting RNA regulatory elements. It is proposed that the promoter driving the expression of the Cx43 gene determines exon choice in the downstream alternative splicing events which in turn affects the efficiency with which the transcript is being translated. Since a similar organization of the Cx43 gene was also observed in rat, it is likely that the complex regulation of Cx43 expression is a common trait and thus, conserved during evolution.

Keywords

Biology, Molecular

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3141884