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Characterization of regulatory intronic and exonic sequences involved in alternative splicing of scavenger receptor class B gene
Authors:Zhang Xiaohui  Merkler Kathleen A  McLean Mark P
Institution:a Department of Obstetrics & Gynecology, University of South Florida College of Medicine, 12901 Bruce B Downs Boulevard, MDC 37, Tampa, FL 33612, USA
b Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, FL 33612, USA
Abstract:Scavenger receptor class B type I (SR-BI) is a major receptor of the high-density lipoprotein that mediates cholesterol efflux and reverse cholesterol transport. Alternative splicing of the scavenger receptor class B (SR-B) gene is observed and different splice forms, SR-BI and scavenger receptor class B type II (SR-BII), have been shown to function and localize in distinct ways. We have previously shown that SR-B alternative splicing regulation is associated with splicing factor ASF/SF2. In this study, using a SR-B minigene as a model, we determined the critical regulatory regions in the upstream intron, intron 11, by serial deletion and mutation analyses. We also further characterized the regulatory elements in intron 11 as well as in the skipped exon, exon 12. Moreover, we studied the interactions of these elements with the splicing factor ASF/SF2. This study provides new insights into the mechanism of SR-B splicing and it is important for further study on the mechanism of SR-B alternative splicing regulation, such as its regulation by estrogen.
Keywords:Scavenger receptor class B  High-density lipoprotein receptor  Alternative splicing  cis-regulatory element  Splicing factor
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