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PNAS | April 16, 2002 | vol. 99 | no. 8 | 5331-5336

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Biochemistry
The frameshift signal of HIV-1 involves a potential intramolecular triplex RNA structure

Jonathan D. Dinman*,dagger , Sara RichterDagger , Ewan P. Plant*, Ronald C. Taylor§, Amy B. Hammell,||, and Tariq M. Ranadagger ,Dagger

* Department of Cell Biology and Molecular Genetics, 2135 Microbiology Building, University of Maryland, College Park, MD 20742; Dagger  Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605-2324;  Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854; and § Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262

Communicated by Reed B. Wickner, National Institutes of Health, Bethesda, MD, February 21, 2002 (received for review October 29, 2001)

The cis-acting mRNA elements that promote programmed -1 ribosomal frameshifting present a natural target for the rational design of antiretroviral chemotherapies. It has been commonly accepted that the HIV-1 frameshifting signal is special, because its downstream enhancer element consists of a simple mRNA stem loop rather than a more complex secondary structure such as a pseudoknot. Here we present three lines of evidence, bioinformatic, structural, and genetic, showing that the biologically relevant HIV-1 frameshift signal contains a complex RNA structure that likely includes an extended RNA triple-helix region. We suggest that the potential intramolecular triplex structure is essential for viral propagation and viability, and that small molecules targeted to this RNA structure may possess antiretroviral activities.


dagger To whom reprint requests may be addressed. E-mail: jd280{at}umail.umd.edu or Tariq.Rana{at}umassmed.edu.

|| Present address: Oncology Department, Novartis, 556 Morris Avenue, LSB 3630, Summit, NJ 07901-1398.

www.pnas.org/cgi/doi/10.1073/pnas.082102199
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