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


EMBO J. 1999 Jul 15;18(14):4060-7. Unique Identifier : AIDSLINE

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.

JOURNAL ARTICLE Base Sequence Binding Sites Cell Nucleus/GENETICS Exons/GENETICS Gene Expression Regulation, Viral Gene Products, tat/*GENETICS Hela Cells Human HIV-1/*GENETICS Mutation Nuclear Proteins/CHEMISTRY/GENETICS/METABOLISM Recombinant Proteins/CHEMISTRY/GENETICS/METABOLISM Regulatory Sequences, Nucleic Acid/GENETICS Ribonucleoproteins/CHEMISTRY/GENETICS/*METABOLISM *RNA Splicing RNA-Binding Proteins/CHEMISTRY/GENETICS/METABOLISM RNA, Messenger/ANALYSIS/GENETICS/*METABOLISM RNA, Viral/ANALYSIS/GENETICS/*METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.


Information in this article was accurate in November 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.