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The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element.
EMBO J. 2001 Oct 15; 20(20):5748-58.EJ

Abstract

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.

Authors+Show Affiliations

Department of Molecular and Structural Biology, University of Aarhus, C.F. Møllers Allé, Building 130, DK-8000 Arhus C, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11598017

Citation

Tange, T O., et al. "The hnRNP A1 Protein Regulates HIV-1 Tat Splicing Via a Novel Intron Silencer Element." The EMBO Journal, vol. 20, no. 20, 2001, pp. 5748-58.
Tange TO, Damgaard CK, Guth S, et al. The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element. EMBO J. 2001;20(20):5748-58.
Tange, T. O., Damgaard, C. K., Guth, S., Valcárcel, J., & Kjems, J. (2001). The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element. The EMBO Journal, 20(20), 5748-58.
Tange TO, et al. The hnRNP A1 Protein Regulates HIV-1 Tat Splicing Via a Novel Intron Silencer Element. EMBO J. 2001 Oct 15;20(20):5748-58. PubMed PMID: 11598017.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element. AU - Tange,T O, AU - Damgaard,C K, AU - Guth,S, AU - Valcárcel,J, AU - Kjems,J, PY - 2001/10/13/pubmed PY - 2002/1/5/medline PY - 2001/10/13/entrez SP - 5748 EP - 58 JF - The EMBO journal JO - EMBO J VL - 20 IS - 20 N2 - 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. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/11598017/The_hnRNP_A1_protein_regulates_HIV_1_tat_splicing_via_a_novel_intron_silencer_element_ L2 - https://doi.org/10.1093/emboj/20.20.5748 DB - PRIME DP - Unbound Medicine ER -