The HIV-1 Integrase C-Terminal Domain Induces TAR RNA Structural Changes Promoting Tat Binding.
Fiche publication
Date publication
novembre 2022
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr RUFF Marc, Dr NEGRONI Matteo
Tous les auteurs :
Rocchi C, Louvat C, Miele AE, Batisse J, Guillon C, Ballut L, Lener D, Negroni M, Ruff M, Gouet P, Fiorini F
Lien Pubmed
Résumé
Recent evidence indicates that the HIV-1 Integrase (IN) binds the viral genomic RNA (gRNA), playing a critical role in the morphogenesis of the viral particle and in the stability of the gRNA once in the host cell. By combining biophysical, molecular biology, and biochemical approaches, we found that the 18-residues flexible C-terminal tail of IN acts as a sensor of the peculiar apical structure of the trans-activation response element RNA (TAR), interacting with its hexaloop. We show that the binding of the whole IN C-terminal domain modifies TAR structure, exposing critical nucleotides. These modifications favour the subsequent binding of the HIV transcriptional trans-activator Tat to TAR, finally displacing IN from TAR. Based on these results, we propose that IN assists the binding of Tat to TAR RNA. This working model provides a mechanistic sketch accounting for the emerging role of IN in the early stages of proviral transcription and could help in the design of anti-HIV-1 therapeutics against this new target of the viral infectious cycle.
Mots clés
C-terminal tail, HIV-1 Integrase, RNA-protein interaction, TAR RNA, Tat, proviral transcription
Référence
Int J Mol Sci. 2022 11 8;23(22):