Insights into the selective activation of alternatively used splice acceptors by the human immunodeficiency virus type-1 bidirectional splicing enhancer.

Nucleic Acids Research
Corinna AsangHeiner Schaal

Abstract

The guanosine-adenosine-rich exonic splicing enhancer (GAR ESE) identified in exon 5 of the human immunodeficiency virus type-1 (HIV-1) pre-mRNA activates either an enhancer-dependent 5' splice site (ss) or 3' ss in 1-intron reporter constructs in the presence of the SR proteins SF2/ASF2 and SRp40. Characterizing the mode of action of the GAR ESE inside the internal HIV-1 exon 5 we found that this enhancer fulfils a dual splicing regulatory function (i) by synergistically mediating exon recognition through its individual SR protein-binding sites and (ii) by conferring 3' ss selectivity within the 3' ss cluster preceding exon 5. Both functions depend upon the GAR ESE, U1 snRNP binding at the downstream 5' ss D4 and the E42 sequence located between these elements. Therefore, a network of cross-exon interactions appears to regulate splicing of the alternative exons 4a and 5. As the GAR ESE-mediated activation of the upstream 3' ss cluster also is essential for the processing of intron-containing vpu/env-mRNAs during intermediate viral gene expression, the GAR enhancer substantially contributes to the regulation of viral replication.

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Citations

Aug 5, 2009·Nucleic Acids Research·Margherita DoriaAlessandro Michienzi
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Jonathan Karn, C Martin Stoltzfus
Dec 21, 2012·Journal of Virology·Marek WideraHeiner Schaal
Apr 5, 2013·PLoS Pathogens·Raymond W WongAlan Cochrane
Aug 26, 2014·Nucleic Acids Research·Steffen ErkelenzHeiner Schaal
Aug 12, 2009·Journal of Cancer Research and Clinical Oncology·Beate BetzBrigitte Royer-Pokora
Apr 11, 2013·DNA Repair·Sari NeijenhuisAlan Ashworth
Sep 12, 2015·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Fazle Elahi FaisalTijana Milenkovic
Apr 19, 2015·Retrovirology·Steffen ErkelenzHeiner Schaal
Jan 8, 2015·Current Opinion in HIV and AIDS·Alex HarwigBen Berkhout
Jan 13, 2017·Journal of Virology·Ann EmeryRonald Swanstrom
Dec 9, 2008·The Biochemical Journal·Jennifer C Long, Javier F Caceres
Mar 6, 2019·International Journal of Molecular Sciences·Frank HillebrandHeiner Schaal
Dec 3, 2016·Biochemical Society Transactions·Charlotte Mahiet, Chad M Swanson
Jan 1, 2017·Nucleic Acids Research·Anna-Lena BrillenHeiner Schaal
Dec 10, 2020·Genome Biology·Simon M HoserAlexander Huettenhofer

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Methods Mentioned

BETA
PCR
transfection
Fluorescence
FCS
ELISA

Software Mentioned

ESEfinder
GAR
P2

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