Journal article

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

Georges Khoury, Charlene Mackenzie, Lilia Ayadi, Sharon R Lewin, Christiane Branlant, Damian FJ Purcell

Nucleic Acids Research | OXFORD UNIV PRESS | Published : 2020

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..

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by National Agency for Research on AIDS and Hepatitis (ANRS)


Awarded by NHMRC


Funding Acknowledgements

National Health and Medical Research Council of Australia (NHMRC) program and project grants [1052979, 1129320 to D.FJ.P.]; National Agency for Research on AIDS and Hepatitis (ANRS) [05195-06194, 08061-09069 to C.B.]; G.K. was a fellow of the french `Minist`ere de la Recherche et de l'Enseignement' and the Sidaction and Pierre Berg ' e foundation. Funding for open access charge: NHMRC project grant [1129320].