Journal ArticleDOI
HIV-1 TAR RNA: the target of molecular interactions between the virus and its host.
Sylvie Bannwarth,Anne Gatignol +1 more
TLDR
HIV-1 TAR RNA is the binding site of the viral protein Tat, the trans-activator of the HIV-1 LTR, which has a highly folded stem-bulge-loop structure, which also binds cellular proteins to form ribonucleoprotein complexes.Abstract:
HIV-1 TAR RNA is the binding site of the viral protein Tat, the trans-activator of the HIV-1 LTR. It is present at the 5' end of all HIV-1 spliced and unspliced mRNAs in the nucleus as well as in the cytoplasm. It has a highly folded stem-bulge-loop structure, which also binds cellular proteins to form ribonucleoprotein complexes. The Tat-Cyclin T1-CDK9 complex is the main component in the trans-activation of HIV-1 and its affinity for TAR is regulated through Tat acetylation by histone acetyl transferases. Recent studies show that this complex is able to recruit other cellular partners to mediate efficient transcriptional elongation. TRBP, PKR and La bind directly to the TAR RNA structure and influence translation of HIV-1 in either positive or negative manners. Some mutations in TAR RNA severely impair HIV-1 trans-activation, translation and viral production, showing its functional importance. The overexpression or suppression of several TAR RNA- binding proteins has a strong impact on viral replication pointing out their major role in the viral life cycle. TAR RNA has been the target of drug development to inhibit viral replication. Recent data using small molecules or RNA-based technologies show that acting on the TAR RNA or on its viral and cellular binding factors effectively decreases virion production.read more
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Journal ArticleDOI
Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action
María Ángel García,Jesús Gil,Iván Ventoso,Susana Guerra,Esteban Domingo,Carmen Rivas,Mariano Esteban +6 more
TL;DR: A detailed picture is provided on how signaling downstream of PKR unfolds and what are the ultimate consequences of the antiproliferative and antiviral effects exerted by interferons.
Journal ArticleDOI
DOCK 6: Combining techniques to model RNA–small molecule complexes
P. Therese Lang,Scott R. Brozell,Sudipto Mukherjee,Eric F. Pettersen,Elaine C. Meng,Veena Thomas,Robert C. Rizzo,David A. Case,Thomas L. James,Irwin D. Kuntz +9 more
TL;DR: A test set of RNA-ligand complexes is compiled to validate the ability of the DOCK suite of programs to successfully recreate experimentally determined binding poses and indicates that DOCK can indeed be useful for structure-based drug design aimed at RNA.
Journal ArticleDOI
Structural Determinants and Mechanism of HIV-1 Genome Packaging
TL;DR: Efforts to identify the molecular determinants and mechanism of human immunodeficiency virus type 1 genome packaging are reviewed.
Journal ArticleDOI
DEAD‐box protein DDX3 associates with eIF4F to promote translation of selected mRNAs
Ricardo Soto-Rifo,Ricardo Soto-Rifo,Paulina S. Rubilar,Paulina S. Rubilar,Taran Limousin,Taran Limousin,Sylvain de Breyne,Sylvain de Breyne,Didier Decimo,Didier Decimo,Théophile Ohlmann,Théophile Ohlmann +11 more
TL;DR: It is demonstrated that the requirement for DDX3 is highly specific to some selected transcripts, cannot be replaced or substituted by eIF4A and is only needed in the very early steps of ribosome binding and prior to 43S ribosomal scanning, defining an unprecedented role for a DEAD‐box RNA helicase in translation initiation.
Journal ArticleDOI
Visualizing transient low-populated structures of RNA
Elizabeth A. Dethoff,Katja Petzold,Jeetender Chugh,Anette Casiano-Negroni,Hashim M. Al-Hashimi +4 more
TL;DR: Nuclear magnetic resonance visualization of RNA transitions towards ‘invisible’ excited states (ESs) is reported, which exist in too little abundance and for too short a duration to allow structural characterization by conventional techniques.