Human Immunodeficiency Virus Type 1 hnRNP A/B-Dependent Exonic Splicing Silencer ESSV Antagonizes Binding of U2AF65 to Viral Polypyrimidine Tracts

Jeffrey K. Domsic, Yibin Wang, Akira Maeda, Adrian R. Krainer, C. Martin Stoltzfus

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1) exonic splicing silencers (ESSs) inhibit production of certain spliced viral RNAs by repressing alternative splicing of the viral precursor RNA. Several HIV-1 ESSs interfere with spliceosome assembly by binding cellular hnRNP A/B proteins. Here, we have further characterized the mechanism of splicing repression using a representative HIV-1 hnRNP A/B-dependent ESS, ESSV, which regulates splicing at the vpr 3′ splice site. We show that hnRNP A/B proteins bound to ESSV are necessary to inhibit E complex assembly by competing with the binding of U2AF65 to the polypyrimidine tracts of repressed 3′ splice sites. We further show evidence suggesting that U1 snRNP binds the 5′ splice site despite an almost complete block of splicing by ESSV. Possible splicing-independent functions of U1 snRNP-5′ splice site interactions during virus replication are discussed.

Original languageEnglish
Pages (from-to)8762-8772
Number of pages11
JournalMolecular and Cellular Biology
Volume23
Issue number23
DOIs
Publication statusPublished - 01-12-2003

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Heterogeneous-Nuclear Ribonucleoproteins
RNA Splice Sites
HIV-1
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
U1 Small Nuclear Ribonucleoproteins
Viral RNA
Spliceosomes
Alternative Splicing
Virus Replication

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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Human Immunodeficiency Virus Type 1 hnRNP A/B-Dependent Exonic Splicing Silencer ESSV Antagonizes Binding of U2AF65 to Viral Polypyrimidine Tracts. / Domsic, Jeffrey K.; Wang, Yibin; Maeda, Akira; Krainer, Adrian R.; Stoltzfus, C. Martin.

In: Molecular and Cellular Biology, Vol. 23, No. 23, 01.12.2003, p. 8762-8772.

Research output: Contribution to journalArticle

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