hnRNP A/B proteins are required for inhibition of HIV-1 pre-mRNA splicing

Massimo Caputi, Akira Maeda, Adrian R. Krainer, Alan M. Zahler

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

Splicing of the human immunodeficiency virus type 1 (HIV-1) pre-mRNA must be inefficient to provide a pool of unspliced messages which encode viral proteins and serve as genomes for new virions. Negative cis-regulatory elements (exonic splicing silencers or ESSs) are necessary for HIV-1 splicing inhibition. We demonstrate that heterogeneous nuclear ribonucleoproteins (hnRNPs) of the A and B group are trans-acting factors required for the function of the tat exon 2 ESS. Depletion of hnRNP A/B proteins from HeLa cell nuclear extract activates splicing of tat exon 2 pre-mRNA substrate. Splicing inhibition is restored by addition of recombinant hnRNP A/B proteins to the depleted extract. A high-affinity hnRNP A1-binding sequence can substitute functionally for the ESS in tat exon 2. These results demonstrate that hnRNP A/B proteins are required for repression of HIV-1 splicing.

Original languageEnglish
Pages (from-to)4060-4067
Number of pages8
JournalEMBO Journal
Volume18
Issue number14
DOIs
Publication statusPublished - 15-07-1999

Fingerprint

Heterogeneous-Nuclear Ribonucleoprotein Group A-B
RNA Precursors
Viruses
HIV-1
Exons
Trans-Activators
Viral Proteins
Cell Extracts
HeLa Cells
Virion
Genes
Genome
Substrates

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

Caputi, Massimo ; Maeda, Akira ; Krainer, Adrian R. ; Zahler, Alan M. / hnRNP A/B proteins are required for inhibition of HIV-1 pre-mRNA splicing. In: EMBO Journal. 1999 ; Vol. 18, No. 14. pp. 4060-4067.
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hnRNP A/B proteins are required for inhibition of HIV-1 pre-mRNA splicing. / Caputi, Massimo; Maeda, Akira; Krainer, Adrian R.; Zahler, Alan M.

In: EMBO Journal, Vol. 18, No. 14, 15.07.1999, p. 4060-4067.

Research output: Contribution to journalArticle

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