The double‐stranded RNA‐binding motif, a versatile macromolecular docking platform

Chang, Kai-Hsiang; Ramos, Andrés

doi:10.1111/j.1742-4658.2005.04652.x

Cited by 114 publications

(108 citation statements)

References 62 publications

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“…The dsRNA binding motif is known to be a versatile macromolecular interaction platform that can in some cases also interact with DNA and proteins (for review, see Ref. 33). dsRNA-BDs are known to heterodimerize with other dsRNA-BDs and to also recognize structurally different protein targets.…”

Section: Discussionmentioning

confidence: 99%

The Double-stranded RNA Binding Domain of the Vaccinia Virus E3L Protein Inhibits Both RNA- and DNA-induced Activation of Interferon β

Marq

Hausmann

Luban

et al. 2009

Journal of Biological Chemistry

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Vaccinia virus, a large DNA virus that replicates in the cytoplasm, expresses its E3L protein to inhibit the cellular innate immune response and apoptosis. E3L is a bifunctional protein that contains an N-terminal DNA binding domain (BD) and a C-terminal double-stranded RNA (dsRNA)-BD (residues 100 -190), both of which contribute to viral pathogenesis by blocking the activation of cellular genes that respond to the viral infection. We report that expression of the dsRNA-BD alone inhibits not only the dsRNA-induced activation of interferon ␤ (IFN␤) but also that of 5-triphosphate single-stranded RNA and DNAinduced IFN␤ activation even though E3L 100 -190 does not bind the latter two pathogen-associated molecular patterns. This inhibition occurs in both human HeLa and A549 cells, where RIG-I appears to be required for dsDNA-induced IFN␤ activation. Unexpectedly, the two residues most important for dsRNA binding are also critical for this domain's ability to inhibit all three nucleic acid-induced cellular responses.

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Section: Discussionmentioning

confidence: 99%

The Double-stranded RNA Binding Domain of the Vaccinia Virus E3L Protein Inhibits Both RNA- and DNA-induced Activation of Interferon β

Marq

Hausmann

Luban

et al. 2009

Journal of Biological Chemistry

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“…Increasing the length of the DCV fragment did not further augment the efficiency of suppression of RNAi. dsRBDs are highly conserved and well studied protein domains (Tian et al 2004;Chang and Ramos 2005). To determine whether DCV-1A suppression requires binding to dsRNA, we mutated highly conserved residues within the dsRBD (L28Y and AA80KK) or residues expected to interact with dsRNA based on available structures (E51A and KK73AA) (Fig.…”

Section: The Rnai Suppressor Is a Dsrna-binding Protein Encoded At Thmentioning

confidence: 99%

The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster

Rij¹,

Saleh²,

Berry³

et al. 2006

Genes Dev.

539

554

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Most organisms have evolved defense mechanisms to protect themselves from viruses and other pathogens.Arthropods lack the protein-based adaptive immune response found in vertebrates. Here we show that the central catalytic component of the RNA-induced silencing complex (RISC), the nuclease Argonaute 2 (Ago-2), is essential for antiviral defense in adult Drosophila melanogaster. Ago-2-defective flies are hypersensitive to infection with a major fruit fly pathogen, Drosophila C virus (DCV), and with Cricket Paralysis virus (CrPV). Increased mortality in ago-2 mutant flies was associated with a dramatic increase in viral RNA accumulation and virus titers. The physiological significance of this antiviral mechanism is underscored by our finding that DCV encodes a potent suppressor of RNA interference (RNAi). This suppressor binds long double-stranded RNA (dsRNA) and inhibits Dicer-2-mediated processing of dsRNA into short interfering RNA (siRNA), but does not bind short siRNAs or disrupt the microRNA (miRNA) pathway. Based on these results we propose that RNAi is a major antiviral immune defense mechanism in Drosophila.

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“…The dsRBD is a ~65-75 amino acids domain with specific binding capacity for dsRNA, which is found in many eukaryotic and prokaryotic proteins presenting a large variety of functions [26][27][28][29]. The structures of different dsRBDs have been determined uncovering a mixed α/β fold with a conserved αβββα topology in which the two α-helices are packed against the three-stranded anti-parallel β-sheet [30,31].…”

Section: Introductionmentioning

confidence: 99%

Solution structure of the N-terminal dsRBD of Drosophila ADAR and interaction studies with RNA

2012

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Adenosine deaminases that act on RNA (ADAR) catalyze adenosine to inosine (A-to-I) editing in double-stranded RNA (dsRNA) substrates. Inosine is read as guanosine by the translation machinery; therefore A-to-I editing events in coding sequences may result in recoding genetic information. Whereas vertebrates have two catalytically active enzymes, namely ADAR1 and ADAR2, Drosophila has a single ADAR protein (dADAR) related to ADAR2. The structural determinants controlling substrate recognition and editing of a specific adenosine within dsRNA substrates are only partially understood. Here, we report the solution structure of the N-terminal dsRNA binding domain (dsRBD) of dADAR and use NMR chemical shift perturbations to identify the protein surface involved in RNA binding. Additionally, we show that Drosophila ADAR edits the R/G site in the mammalian GluR-2 pre-mRNA which is naturally modified by both ADAR1 and ADAR2. We then constructed a model showing how dADAR dsRBD1 binds to the GluR-2 R/G stem-loop. This model revealed that most side chains interacting with the RNA sugar-phosphate backbone need only small displacement to adapt for dsRNA binding and are thus ready to bind to their dsRNA target. It also predicts that dADAR dsRBD1 would bind to dsRNA with less sequence specificity than dsRBDs of ADAR2. Altogether, this study gives new insights into dsRNA substrate recognition by Drosophila ADAR.

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The double‐stranded RNA‐binding motif, a versatile macromolecular docking platform

Cited by 114 publications

References 62 publications

The Double-stranded RNA Binding Domain of the Vaccinia Virus E3L Protein Inhibits Both RNA- and DNA-induced Activation of Interferon β

The Double-stranded RNA Binding Domain of the Vaccinia Virus E3L Protein Inhibits Both RNA- and DNA-induced Activation of Interferon β

The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster

Solution structure of the N-terminal dsRBD of Drosophila ADAR and interaction studies with RNA

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