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* Department of Cell Biology and Molecular Genetics, 2135 Microbiology Building, University of Maryland, College Park, MD 20742;
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
Biochemistry
The frameshift signal of HIV-1 involves a potential
intramolecular triplex RNA structure
,
,
, and
,
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
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.
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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