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SR proteins and hnRNP H regulate the splicing of the HIV-1 tev-specific exon 6D.
EMBO J. 2002 Feb 15; 21(4):845-55.EJ

Abstract

A naturally arising point mutation in the env gene of HIV-1 activates the aberrant inclusion of the cryptic exon 6D into most viral messages, leading to inefficient viral replication. We set out to understand how a single nucleotide substitution could cause such a dramatic change in splicing. We have determined that the exon 6D mutation promotes binding of the SR protein SC35 to the exon. Mutant exon 6D sequences function as a splicing enhancer when inserted into an enhancer-dependent splicing construct. hnRNP H family proteins bind to the enhancer as well; their binding is dependent on the sequence GGGA located just downstream of the point mutation and depletion-- reconstitution studies show that hnRNP H is essential for enhancer activity. A polypurine sequence located further downstream in exon 6D binds SR proteins but acts as an exonic splicing silencer. hnRNP H is required for interaction of U1 snRNP with the enhancer, independent of the point mutation. We propose that SC35 binding to the point mutation region may convert the hnRNP H-U1 snRNP complex into a splicing enhancer.

Authors+Show Affiliations

Department of Molecular, Cell and Developmental Biology, Sinsheimer Laboratory, University of California Santa Cruz, Santa Cruz, CA 95064, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11847131

Citation

Caputi, Massimo, and Alan M. Zahler. "SR Proteins and hnRNP H Regulate the Splicing of the HIV-1 Tev-specific Exon 6D." The EMBO Journal, vol. 21, no. 4, 2002, pp. 845-55.
Caputi M, Zahler AM. SR proteins and hnRNP H regulate the splicing of the HIV-1 tev-specific exon 6D. EMBO J. 2002;21(4):845-55.
Caputi, M., & Zahler, A. M. (2002). SR proteins and hnRNP H regulate the splicing of the HIV-1 tev-specific exon 6D. The EMBO Journal, 21(4), 845-55.
Caputi M, Zahler AM. SR Proteins and hnRNP H Regulate the Splicing of the HIV-1 Tev-specific Exon 6D. EMBO J. 2002 Feb 15;21(4):845-55. PubMed PMID: 11847131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SR proteins and hnRNP H regulate the splicing of the HIV-1 tev-specific exon 6D. AU - Caputi,Massimo, AU - Zahler,Alan M, PY - 2002/2/16/pubmed PY - 2002/4/20/medline PY - 2002/2/16/entrez SP - 845 EP - 55 JF - The EMBO journal JO - EMBO J VL - 21 IS - 4 N2 - A naturally arising point mutation in the env gene of HIV-1 activates the aberrant inclusion of the cryptic exon 6D into most viral messages, leading to inefficient viral replication. We set out to understand how a single nucleotide substitution could cause such a dramatic change in splicing. We have determined that the exon 6D mutation promotes binding of the SR protein SC35 to the exon. Mutant exon 6D sequences function as a splicing enhancer when inserted into an enhancer-dependent splicing construct. hnRNP H family proteins bind to the enhancer as well; their binding is dependent on the sequence GGGA located just downstream of the point mutation and depletion-- reconstitution studies show that hnRNP H is essential for enhancer activity. A polypurine sequence located further downstream in exon 6D binds SR proteins but acts as an exonic splicing silencer. hnRNP H is required for interaction of U1 snRNP with the enhancer, independent of the point mutation. We propose that SC35 binding to the point mutation region may convert the hnRNP H-U1 snRNP complex into a splicing enhancer. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/11847131/SR_proteins_and_hnRNP_H_regulate_the_splicing_of_the_HIV_1_tev_specific_exon_6D_ L2 - https://doi.org/10.1093/emboj/21.4.845 DB - PRIME DP - Unbound Medicine ER -