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PMID: 11959986 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 8 ·2002-04-16 ·Pages 5331-6

Dinman JD, Richter S, Plant EP, Taylor RC, Hammell AB, Rana TM

Abstract

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.

MeSH Terms
Anti-HIV Agents/pharmacology Base Sequence DNA Databases as Topic Frameshift Mutation HIV-1/genetics HeLa Cells Humans Molecular Sequence Data Nucleic Acid Conformation Plasmids/metabolism RNA/metabolism RNA, Messenger/metabolism Ribonucleases/metabolism Structure-Activity Relationship Yeasts/metabolism
Chemicals
Anti-HIV Agents RNA, Messenger triplex DNA RNA DNA Ribonucleases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Dinman Jonathan D
Department of Cell Biology and Molecular Genetics, 2135 Microbiology Building, University of Maryland, College Park, MD 20742, USA. jd280@umail.umd.edu
Richter Sara
Plant Ewan P
Taylor Ronald C
Hammell Amy B
Rana Tariq M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.082102199
Email
jd280@umail.umd.edu
Published
2002-04-16
Pages
5331-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC122769
Subset
IM
Grants
NIAID NIH HHS · R01 AI043198 · United States
NIGMS NIH HHS · R01 GM058859 · United States
NIDA NIH HHS · R01 DA030199 · United States
NIAID NIH HHS · AI 43198 · United States
NIGMS NIH HHS · GM 58859 · United States
NIAID NIH HHS · AI 45466 · United States
External Links
PubMed source DOI: 10.1073/pnas.082102199 PMC Full Text View journal details
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