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SC35 and heterogeneous nuclear ribonucle ... ulate HIV-1 tat exon 2 splicing
SC35 and heterogeneous nuclear ribonucleoprotein AB proteins bind to a juxtaposed exonic splicing enhancerexonic splicing silencer element to regulate HIV-1 tat exon 2 splicing
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Splicing of the human immunodeficiency virus, type 1, primary transcript is highly regulated. Maintaining the proper equilibrium among spliced, unspliced, and partially spliced isoforms is essential for the replication of the virus. Here we characterize a complex cis-acting element located in tat exon 2 that is required for the splicing regulation of the upstream intron. An exonic splicing enhancer (ESE) and an exonic splicing silencer (ESS) are both located within the regulatory element. Heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins bind the ESS to repress splicing, whereas the SR protein SC35 binds the ESE to activate it. We show that the SC35 and the hnRNP A1 binding sites overlap within the juxtaposed ESE/ESS. We propose that hnRNP A1 binding to the ESS inhibits splicing of the upstream intron by directly masking the SC35 binding site.
Zahler AM, Damgaard CK, Kjems J, Caputi M
The Journal of biological chemistry
2004-03-12 00:00
279
11
10077-84
Base Sequence,Binding Sites,Cell Nucleus,Chromatography,Electrophoresis, Polyacrylamide Gel,Exons,Gene Expression Regulation,Gene Products, tat,Gene Silencing,Hela Cells,Heterogeneous-Nuclear Ribonucleoprotein Group A-B,Heterogeneous-Nuclear Ribonucleoproteins,Humans,Introns,Models, Biological,Models, Genetic,Molecular Sequence Data,Nuclear Proteins,Plasmids,Protein Binding,RNA,RNA Splicing,RNA, Messenger,Recombinant Proteins,Ribonucleoproteins,Gene Products, tat,Heterogeneous-Nuclear Ribonucleoprotein Group A-B,Heterogeneous-Nuclear Ribonucleoproteins,Nuclear Proteins,RNA, Messenger,Recombinant Proteins,Ribonucleoproteins,heterogeneous nuclear ribonucleoprotein A2-B1,hnRNP A1,SFRS2 protein, human,RNA
Department of Molecular, Cellular and Developmental Biology and Center for Molecular Biology of RNA, Sinsheimer Laboratories, University of California, Santa Cruz 95064, USA.
J. Biol. Chem.
NIGMS 1R01GM61646, NIAID 5R01AI052820-02
0021-9258
10.1074/jbc.M312743200
M312743200
0
False
14703516
