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Tra2-mediated recognition of HIV-1 5' splice site D3 as a key factor in the processing of vpr mRNA.
J Virol. 2013 Mar; 87(5):2721-34.JV

Abstract

Small noncoding HIV-1 leader exon 3 is defined by its splice sites A2 and D3. While 3' splice site (3'ss) A2 needs to be activated for vpr mRNA formation, the location of the vpr start codon within downstream intron 3 requires silencing of splicing at 5'ss D3. Here we show that the inclusion of both HIV-1 exon 3 and vpr mRNA processing is promoted by an exonic splicing enhancer (ESE(vpr)) localized between exonic splicing silencer ESSV and 5'ss D3. The ESE(vpr) sequence was found to be bound by members of the Transformer 2 (Tra2) protein family. Coexpression of these proteins in provirus-transfected cells led to an increase in the levels of exon 3 inclusion, confirming that they act through ESE(vpr). Further analyses revealed that ESE(vpr) supports the binding of U1 snRNA at 5'ss D3, allowing bridging interactions across the upstream exon with 3'ss A2. In line with this, an increase or decrease in the complementarity of 5'ss D3 to the 5' end of U1 snRNA was accompanied by a higher or lower vpr expression level. Activation of 3'ss A2 through the proposed bridging interactions, however, was not dependent on the splicing competence of 5'ss D3 because rendering it splicing defective but still competent for efficient U1 snRNA binding maintained the enhancing function of D3. Therefore, we propose that splicing at 3'ss A2 occurs temporally between the binding of U1 snRNA and splicing at D3.

Authors+Show Affiliations

Institute for Virology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

23255807

Citation

Erkelenz, Steffen, et al. "Tra2-mediated Recognition of HIV-1 5' Splice Site D3 as a Key Factor in the Processing of Vpr MRNA." Journal of Virology, vol. 87, no. 5, 2013, pp. 2721-34.
Erkelenz S, Poschmann G, Theiss S, et al. Tra2-mediated recognition of HIV-1 5' splice site D3 as a key factor in the processing of vpr mRNA. J Virol. 2013;87(5):2721-34.
Erkelenz, S., Poschmann, G., Theiss, S., Stefanski, A., Hillebrand, F., Otte, M., Stühler, K., & Schaal, H. (2013). Tra2-mediated recognition of HIV-1 5' splice site D3 as a key factor in the processing of vpr mRNA. Journal of Virology, 87(5), 2721-34. https://doi.org/10.1128/JVI.02756-12
Erkelenz S, et al. Tra2-mediated Recognition of HIV-1 5' Splice Site D3 as a Key Factor in the Processing of Vpr MRNA. J Virol. 2013;87(5):2721-34. PubMed PMID: 23255807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tra2-mediated recognition of HIV-1 5' splice site D3 as a key factor in the processing of vpr mRNA. AU - Erkelenz,Steffen, AU - Poschmann,Gereon, AU - Theiss,Stephan, AU - Stefanski,Anja, AU - Hillebrand,Frank, AU - Otte,Marianne, AU - Stühler,Kai, AU - Schaal,Heiner, Y1 - 2012/12/19/ PY - 2012/12/21/entrez PY - 2012/12/21/pubmed PY - 2013/4/25/medline SP - 2721 EP - 34 JF - Journal of virology JO - J. Virol. VL - 87 IS - 5 N2 - Small noncoding HIV-1 leader exon 3 is defined by its splice sites A2 and D3. While 3' splice site (3'ss) A2 needs to be activated for vpr mRNA formation, the location of the vpr start codon within downstream intron 3 requires silencing of splicing at 5'ss D3. Here we show that the inclusion of both HIV-1 exon 3 and vpr mRNA processing is promoted by an exonic splicing enhancer (ESE(vpr)) localized between exonic splicing silencer ESSV and 5'ss D3. The ESE(vpr) sequence was found to be bound by members of the Transformer 2 (Tra2) protein family. Coexpression of these proteins in provirus-transfected cells led to an increase in the levels of exon 3 inclusion, confirming that they act through ESE(vpr). Further analyses revealed that ESE(vpr) supports the binding of U1 snRNA at 5'ss D3, allowing bridging interactions across the upstream exon with 3'ss A2. In line with this, an increase or decrease in the complementarity of 5'ss D3 to the 5' end of U1 snRNA was accompanied by a higher or lower vpr expression level. Activation of 3'ss A2 through the proposed bridging interactions, however, was not dependent on the splicing competence of 5'ss D3 because rendering it splicing defective but still competent for efficient U1 snRNA binding maintained the enhancing function of D3. Therefore, we propose that splicing at 3'ss A2 occurs temporally between the binding of U1 snRNA and splicing at D3. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/23255807/Tra2_mediated_recognition_of_HIV_1_5'_splice_site_D3_as_a_key_factor_in_the_processing_of_vpr_mRNA_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=23255807 DB - PRIME DP - Unbound Medicine ER -