The HIV-1 Integrase C-Terminal Domain Induces TAR RNA Structural Changes Promoting Tat Binding

Autor: Cecilia Rocchi, Camille Louvat, Patrice Gouet, Daniela Lener, Matteo Negroni, Lionel Ballut, Adriana Miele, Francesca Fiorini, Marc Ruff, Christophe Guillon, Julien Batisse
Přispěvatelé: Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BioSciences Lyon-Gerland (BLG), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Fiorini, Francesca
Rok vydání: 2022
Předmět:
RNA-protein interaction
[SDV]Life Sciences [q-bio]
Response element
Morphogenesis
HIV Integrase
Catalysis
Inorganic Chemistry
03 medical and health sciences
Tar (tobacco residue)
Transcription (biology)
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
TAR RNA
Guide RNA
Physical and Theoretical Chemistry
Molecular Biology
Spectroscopy
030304 developmental biology
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
0303 health sciences
biology
HIV-1 Integrase
Tat
proviral transcription
C-terminal tail
Chemistry
C-terminus
030302 biochemistry & molecular biology
Organic Chemistry
RNA
General Medicine
3. Good health
Cell biology
Integrase
Computer Science Applications
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
biology.protein
RNA
Viral
tat Gene Products
Human Immunodeficiency Virus
RNA
Guide
Kinetoplastida
Transcription Factors
Zdroj: International Journal of Molecular Sciences; Volume 23; Issue 22; Pages: 13742
HAL
International Journal of Molecular Sciences
International Journal of Molecular Sciences, 2022, 23 (22), pp.13742. ⟨10.3390/ijms232213742⟩
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms232213742
Popis: International audience; 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje