SC35 and heterogeneous nuclear ribonucleoprotein A/B proteins bind to a juxtaposed exonic splicing enhancer/exonic splicing silencer element to regulate HIV-1 tat exon 2 splicing

Alan M Zahler, Christian K Damgaard, Jørgen Kjems, Massimo Caputi

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalJournal of Biological Chemistry
Volume279
Issue11
Pages (from-to)10077-10084
Number of pages8
ISSN0021-9258
DOIs
Publication statusPublished - 12 Mar 2004

Keywords

  • 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

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