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

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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.