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.
Nucleic Acids Res
; 48(5): 2643-2660, 2020 03 18.
Article
in En
| MEDLINE
| ID: mdl-31875221
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Viral
/
HIV Infections
/
HIV-1
/
Conserved Sequence
/
Virus Latency
/
Tat Gene Products, Human Immunodeficiency Virus
/
Internal Ribosome Entry Sites
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2020
Type:
Article
Affiliation country:
Australia