18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

THE STRUCTURE OF AN ENTIRE HIV-1 RNA GENOME

Antivir Ther 2009; 14 Suppl 1:A30 (abstract no. 28)

JM Watts, KA Wilkinson, RJ Gorelick and KM Weeks
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

HIV replication is regulated at many levels, including using essential, conserved genomic RNA structures to exploit and circumvent host biology. However, the vast majority of potential regulatory elements within the HIV RNA genome are uncharacterized. We used high-throughput SHAPE (selective 2´-hydroxyl acylation analyzed by primer extension) to quantify RNA backbone flexibility at single-nucleotide resolution for an entire HIV-1 genome. From this analysis, robust structural information and select structure-function relationships can be immediately derived. We detected specific protein-RNA interactions inside HIV virions and identifed three RNA binding functions for the viral nucleocapsid protein. There was a strong correlation between the overall level of RNA structure, as determined by SHAPE, and the propensity of a given genome region to have a regulatory function that was beyond simply coding for viral proteins. The HIV-1 genome, and potentially most large coding RNAs, is punctuated by numerous previously unrecognized, but conserved, RNA regulatory motifs. High-throughput SHAPE reveals a comprehensive view of HIV-1 RNA genome structure and further application of this technology will make possible newly informative analysis of any RNA in a cellular transcriptome.

2009-06-09
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