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

被引：7

作者：

Rocchi, Cecilia ^{[1
]}

Louvat, Camille ^{[1
]}

Miele, Adriana Erica ^{[2
,3
]}

Batisse, Julien ^{[4
]}

Guillon, Christophe ^{[1
]}

Ballut, Lionel ^{[1
]}

Lener, Daniela ^{[5
]}

Negroni, Matteo ^{[5
]}

Ruff, Marc ^{[4
]}

Gouet, Patrice ^{[1
]}

Fiorini, Francesca ^{[1
]}

机构：

[1] Univ Lyon, CNRS, UMR 5086, Mol Microbiol & Struct Biochem,MMSB IBCP, 7 Passage Vercors, F-69367 Lyon 07, France

[2] Univ Lyon, Inst Analyt Sci, UMR 5280, CNRS,UCBL, 5 Rue Doua, F-69100 Villeurbanne, France

[3] Sapienza Univ Rome, Dept Biochem Sci, Ple Aldo Moro 5, I-00185 Rome, Italy

[4] Univ Strasbourg, INSERM, U158,IGBMC,CNRS,UMR 7104, Chromatin Stabil & DNA Mobil,Dept Integrated Stru, 1 Rue Laurent Fries, F-67404 Illkirch Graffenstaden, France

[5] Univ Strasbourg, UPR 9002, RNA Architecture & React, CNRS,IBMC, 2 Allee Konrad Roentgen, F-67084 Strasbourg, France

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2022年 / 23卷 / 22期

关键词：

RNA-protein interaction; HIV-1; Integrase; TAR RNA; Tat; proviral transcription; C-terminal tail; IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSCRIPTION ELONGATION; HIGH-AFFINITY; PROTEIN; DNA; RESIDUES; COMPLEX; TRANSACTIVATION; IDENTIFICATION; RECOGNITION;

D O I：

10.3390/ijms232213742

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：18