Tat IRES modulator of tat mRNA (TIM-TAM): a conserved RNA structure that controls Tat expression and acts as a switch for HIV productive and latent infection.
Base Sequence
Conserved Sequence
/ genetics
HIV Infections
/ virology
HIV-1
/ genetics
HeLa Cells
Humans
Internal Ribosome Entry Sites
/ genetics
Models, Biological
Nucleic Acid Conformation
Protein Biosynthesis
Proviruses
/ genetics
RNA, Messenger
/ metabolism
RNA, Viral
/ chemistry
Virus Activation
Virus Latency
/ genetics
tat Gene Products, Human Immunodeficiency Virus
/ metabolism
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 03 2020
18 03 2020
Historique:
accepted:
18
12
2019
revised:
04
12
2019
received:
27
05
2019
pubmed:
26
12
2019
medline:
19
5
2020
entrez:
26
12
2019
Statut:
ppublish
Résumé
Tat protein is essential to fully activate HIV transcription and processing of viral mRNA, and therefore determines virus expression in productive replication and the establishment and maintenance of latent infection. Here, we used thermodynamic and structure analyses to define a highly conserved sequence-structure in tat mRNA that functions as Tat IRES modulator of tat mRNA (TIM-TAM). By impeding cap-dependent ribosome progression during authentic spliced tat mRNA translation, TIM-TAM stable structure impacts on timing and level of Tat protein hence controlling HIV production and infectivity along with promoting latency. TIM-TAM also adopts a conformation that mediates Tat internal ribosome entry site (IRES)-dependent translation during the early phases of infection before provirus integration. Our results document the critical role of TIM-TAM in Tat expression to facilitate virus reactivation from latency, with implications for HIV treatment and drug development.
Identifiants
pubmed: 31875221
pii: 5686799
doi: 10.1093/nar/gkz1181
pmc: PMC7049722
doi:
Substances chimiques
Internal Ribosome Entry Sites
0
RNA, Messenger
0
RNA, Viral
0
tat Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2643-2660Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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