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

Item Type:Article
Title:A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome assembly
Creators Name:Zheng, Z.M. and Huynen, M. and Baker, C.C.
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:Alternative Splicing, Base Sequence, Bovine Papillomavirus 1, Genetic Enhancer Elements, Exons, HIV-1, Hela Cells, Molecular Sequence Data, Site-Directed Mutagenesis, Nuclear Proteins, Nucleic Acid Conformation, Polymerase Chain Reaction, RNA Precursors, Viral RNA, Sequence Deletion, Spliceosomes, Genetic Templates, Genetic Transcription, Animals, Cattle
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:95
Number:24
Page Range:14088-14093
Date:24 November 1998
Official Publication:http://www.pnas.org/content/95/24/14088.abstract
PubMed:View item in PubMed

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