The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding.

Rocchi, C.; Louvat, C.; Miele, A. E.; Batisse, J.; Guillon, C.; Ballut, L.; Lener, D.; Negroni, M.; Ruff, M.; Gouet, P.; Fiorini, F.

doi:10.1101/2021.10.21.465253

bioRxiv · 10.1101/2021.10.21.465253

The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding.

Rocchi, C.·Louvat, C.·Miele, A. E.·Batisse, J.·Guillon, C.·Ballut, L.·Lener, D.·Negroni, M.·Ruff, M.·Gouet, P.·Fiorini, F.

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Abstract

Recent evidence indicated that HIV-1 Integrase (IN) binds genomic viral RNA (gRNA) playing a critical role in viral particle morphogenesis and gRNA stability in host cells. Combining biophysical and biochemical approaches we show that the C-terminal flexible 18-residues tail of IN acts as a sensor of the peculiar apical structure of trans-activation response element RNA (TAR), directly interacting with its hexaloop. We highlighted how the whole IN C-terminal domain, once bound to TAR, can change its structure assisting the binding of Tat, the HIV trans-activator protein, which finally displaces IN from TAR. Our results are consistent with the emerging role of IN in early stage of proviral transcription and suggest new steps of HIV-1 life cycle that can be considered as therapeutic targets.

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Rocchi, C., Louvat, C., Miele, A. E., Batisse, J., Guillon, C., Ballut, L., Lener, D., Negroni, M., Ruff, M., Gouet, P., Fiorini, F.. 2021-10-21. The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding.. https://doi.org/10.1101/2021.10.21.465253

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