translation agency

hnRNP A/B proteins are required for inhibition of HIV-1 pre-mRNA splicing.
Caputi M; Mayeda A; Krainer AR; Zahler AM; Department of Biology and
November 30, 1999
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.