The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element

AUTOR(ES)

Tange, Thomas Ø.

FONTE

Oxford University Press

RESUMO

The generation of >30 different HIV-1 mRNAs is achieved by alternative splicing of one primary transcript. The removal of the second tat intron is regulated by a combination of a suboptimal 3′ splice site and cis-acting splicing enhancers and silencers. Here we show that hnRNP A1 inhibits splicing of this intron via a novel heterogeneous nuclear ribonucleoprotein (hnRNP) A1-responsive intron splicing silencer (ISS) that can function independently of the previously characterized exon splicing silencer (ESS3). Surprisingly, depletion of hnRNP A1 from the nuclear extract (NE) enables splicing to proceed in NE that contains 100-fold reduced concentrations of U2AF and normal levels of SR proteins, conditions that do not support processing of other efficiently spliced pre-mRNAs. Reconstituting the extract with recombinant hnRNP A1 protein restores splicing inhibition at a step subsequent to U2AF binding, mainly at the time of U2 snRNP association. hnRNP A1 interacts specifically with the ISS sequence, which overlaps with one of three alternative branch point sequences, pointing to a model where the entry of U2 snRNP is physically blocked by hnRNP A1 binding.

Documentos Relacionados

• An intron element modulating 5' splice site selection in the hnRNP A1 pre-mRNA interacts with hnRNP A1.
• Control of hnRNP A1 Alternative Splicing: an Intron Element Represses Use of the Common 3′ Splice Site
• hnRNP A1 Recruited to an Exon In Vivo Can Function as an Exon Splicing Silencer
• Alternative splicing in the human gene for the core protein A1 generates another hnRNP protein.
• RNA binding specificity of hnRNP A1: significance of hnRNP A1 high-affinity binding sites in pre-mRNA splicing.