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Journal of Virology, August 2008, p. 8038-8050, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00721-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Secondary Structure of the Human Immunodeficiency Virus Type 1 Transcript Modulates Viral Splicing and Infectivity {triangledown}

Joseph A. Jablonski,1,{dagger} Emanuele Buratti,2,{dagger} Cristiana Stuani,2 and Massimo Caputi1*

Basic Science Department, Florida Atlantic University, Boca Raton, Florida 33431,1 International Centre for Genetic Engineering and Biotechnology, Trieste, Italy2

Received 31 March 2008/ Accepted 29 May 2008

Splicing of human immunodeficiency virus type 1 (HIV-1) exon 6D is regulated by the presence of a complex splicing regulatory element (SRE) sequence that interacts with the splicing factors hnRNP H and SC35. In this work, we show that, in the context of the wild-type viral sequence, hnRNP H acts as a repressor of exon 6D inclusion independent of its binding to the SRE. However, hnRNP H binding to the SRE acts as an enhancer of exon 6D inclusion in the presence of a critical T-to-C mutation. These seemingly contrasting functional properties of hnRNP H appear to be caused by a change in the RNA secondary structure induced by the T-to-C mutation that affects the spatial location of bound hnRNP H with respect to the exon 6D splicing determinants. We propose a new regulatory mechanism mediated by RNA folding that may also explain the dual properties of hnRNP H in splicing regulation.


* Corresponding author. Mailing address: Florida Atlantic University, College of Biomedical Science, 777 Glades Rd., Boca Raton, FL 33431. Phone: (561) 297-0627. Fax: (561) 297-2221. E-mail: mcaputi{at}fau.edu

{triangledown} Published ahead of print on 11 June 2008.

{dagger} J.A.J. and E.B. contributed equally to the work.


Journal of Virology, August 2008, p. 8038-8050, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00721-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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