Publications
2009
Keating C P, Hill M K, Hawkes D J, Smyth R P, Isel C, Le S Y, Palmenberg A C, Marshall J A, Marquet R, Nabel G J, Mak J
The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral cDNA Article de journal
Dans: Nucleic Acids Res, vol. 37, no. 3, p. 945-956, 2009, ISBN: 19106143, (1362-4962 (Electronic) Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't).
Résumé | Liens | BibTeX | Étiquettes: Adenine/analysis Base Sequence Cell Line Codon DNA, Complementary/*biosynthesis DNA, MARQUET, PAILLART, pol HIV-1/*genetics/physiology Humans Nucleic Acid Conformation RNA, Ribonucleic Acid *Reverse Transcription Viral Proteins/metabolism Virion/metabolism Virus Internalization Virus Replication, Unité ARN, Viral/*biosynthesis Dimerization *Genes, Viral/*chemistry *Regulatory Sequences
@article{,
title = {The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral cDNA},
author = {C P Keating and M K Hill and D J Hawkes and R P Smyth and C Isel and S Y Le and A C Palmenberg and J A Marshall and R Marquet and G J Nabel and J Mak},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19106143},
isbn = {19106143},
year = {2009},
date = {2009-01-01},
journal = {Nucleic Acids Res},
volume = {37},
number = {3},
pages = {945-956},
abstract = {The bias of A-rich codons in HIV-1 pol is thought to be a record of hypermutations in viral genomes that lack biological functions. Bioinformatic analysis predicted that A-rich sequences are generally associated with minimal local RNA structures. Using codon modifications to reduce the amount of A-rich sequences within HIV-1 genomes, we have reduced the flexibility of RNA sequences in pol to analyze the functional significance of these A-rich 'structurally poor' RNA elements in HIV-1 pol. Our data showed that codon modification of HIV-1 sequences led to a suppression of virus infectivity by 5-100-fold, and this defect does not correlate with, viral entry, viral protein expression levels, viral protein profiles or virion packaging of genomic RNA. Codon modification of HIV-1 pol correlated with an enhanced dimer stability of the viral RNA genome, which was associated with a reduction of viral cDNA synthesis both during HIV-1 infection and in a cell free reverse transcription assay. Our data provided direct evidence that the HIV-1 A-rich pol sequence is not merely an evolutionary artifact of enzyme-induced hypermutations, and that HIV-1 has adapted to rely on A-rich RNA sequences to support the synthesis of viral cDNA during reverse transcription, highlighting the utility of using 'structurally poor' RNA domains in regulating biological process.},
note = {1362-4962 (Electronic)
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't},
keywords = {Adenine/analysis Base Sequence Cell Line Codon DNA, Complementary/*biosynthesis DNA, MARQUET, PAILLART, pol HIV-1/*genetics/physiology Humans Nucleic Acid Conformation RNA, Ribonucleic Acid *Reverse Transcription Viral Proteins/metabolism Virion/metabolism Virus Internalization Virus Replication, Unité ARN, Viral/*biosynthesis Dimerization *Genes, Viral/*chemistry *Regulatory Sequences},
pubstate = {published},
tppubtype = {article}
}