A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome assembly.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome assembly.

Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14088-93. Unique Identifier : AIDSLINE MED/99045642
Zheng ZM; Huynen M; Baker CC; Basic Research Laboratory, Division of Basic Sciences, National; Cancer Institute, National Institutes of Health, Building 41,; Room D305, Bethesda, MD 20892-5055, USA. zheng@dce41.nci.nih.gov

Abstract: The bovine papillomavirus type 1 (BPV-1) exonic splicing suppressor (ESS) is juxtaposed immediately downstream of BPV-1 splicing enhancer 1 and negatively modulates selection of a suboptimal 3' splice site at nucleotide 3225. The present study demonstrates that this pyrimidine-rich ESS inhibits utilization of upstream 3' splice sites by blocking early steps in spliceosome assembly. Analysis of the proteins that bind to the ESS showed that the U-rich 5' region binds U2AF65 and polypyrimidine tract binding protein, the C-rich central part binds 35- and 54-55-kDa serine/arginine-rich (SR) proteins, and the AG-rich 3' end binds alternative splicing factor/splicing factor 2. Mutational and functional studies indicated that the most critical region of the ESS maps to the central C-rich core (GGCUCCCCC). This core sequence, along with additional nonspecific downstream nucleotides, is sufficient for partial suppression of spliceosome assembly and splicing of BPV-1 pre-mRNAs. The inhibition of splicing by the ESS can be partially relieved by excess purified HeLa SR proteins, suggesting that the ESS suppresses pre-mRNA splicing by interfering with normal bridging and recruitment activities of SR proteins.

Keywords: JOURNAL ARTICLE *Alternative Splicing Animal Base Sequence Cattle Enhancer Elements (Genetics) *Exons Hela Cells Human HIV-1/GENETICS Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/METABOLISM Nucleic Acid Conformation Papillomavirus, Bovine/*GENETICS/METABOLISM Polymerase Chain Reaction RNA Precursors/CHEMISTRY/GENETICS RNA, Viral/CHEMISTRY/GENETICS Sequence Deletion Spliceosomes/GENETICS/METABOLISM Templates Transcription, Genetic
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