Nuclear factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA

Jayachandran, Uma; Grey, Heather; Cook, Atlanta G.

doi:10.1093/nar/gkv1508

Cited by 41 publications

(37 citation statements)

References 51 publications

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“…In case of single-register binding, Ala57 and Ala187 are expected to have a maximum of two intermolecular NOEs, that is, with two consecutive nucleotides. Therefore, we conclude from this multiplicity of NOEs that TRBP's individual domains do not bind EL86 sequence specifically but rather in multiple registers, unlike the dsRBDs of ADAR2 or NF90, which have been shown to bind dsRNA in single registers (Stefl et al, 2010;Jayachandran et al, 2016).…”

Section: Individual Trbp's Dsrbds Bind El86 In Multiple Registersmentioning

confidence: 82%

Structural basis of si RNA recognition by TRBP double‐stranded RNA binding domains

et al. 2018

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The accurate cleavage of pre‐micro(mi)RNAs by Dicer and mi/siRNA guide strand selection are important steps in forming the RNA‐induced silencing complex (RISC). The role of Dicer binding partner TRBP in these processes remains poorly understood. Here, we solved the solution structure of the two N‐terminal dsRNA binding domains (dsRBDs) of TRBP in complex with a functionally asymmetric siRNA using NMR, EPR, and single‐molecule spectroscopy. We find that siRNA recognition by the dsRBDs is not sequence‐specific but rather depends on the RNA shape. The two dsRBDs can swap their binding sites, giving rise to two equally populated, pseudo‐symmetrical complexes, showing that TRBP is not a primary sensor of siRNA asymmetry. Using our structure to model a Dicer‐TRBP‐siRNA ternary complex, we show that TRBP's dsRBDs and Dicer's RNase III domains bind a canonical 19 base pair siRNA on opposite sides, supporting a mechanism whereby TRBP influences Dicer‐mediated cleavage accuracy by binding the dsRNA region of the pre‐miRNA during Dicer cleavage.

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Section: Individual Trbp's Dsrbds Bind El86 In Multiple Registersmentioning

confidence: 82%

Structural basis of si RNA recognition by TRBP double‐stranded RNA binding domains

et al. 2018

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“…Here, we apply the server to investigate the Mg 2+ effects in the binding between NF90 and a double-stranded RNA (dsRNA) helix. With the dsRNA-NF90 complex (PDBID: 5DV7) (Jayachandran et al 2016) and the dsRNA structure (the inset of Fig. 5B), the server gives the Mg 2+ ion-induced free energies.…”

Section: +mentioning

confidence: 99%

MCTBI: a web server for predicting metal ion effects in RNA structures

Sun

Zhang

Chen

2017

RNA

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Metal ions play critical roles in RNA structure and function. However, web servers and software packages for predicting ion effects in RNA structures are notably scarce. Furthermore, the existing web servers and software packages mainly neglect ion correlation and fluctuation effects, which are potentially important for RNAs. We here report a new web server, the MCTBI server (http://rna. physics.missouri.edu/MCTBI), for the prediction of ion effects for RNA structures. This server is based on the recently developed MCTBI, a model that can account for ion correlation and fluctuation effects for nucleic acid structures and can provide improved predictions for the effects of metal ions, especially for multivalent ions such as Mg 2+ effects, as shown by extensive theoryexperiment test results. The MCTBI web server predicts metal ion binding fractions, the most probable bound ion distribution, the electrostatic free energy of the system, and the free energy components. The results provide mechanistic insights into the role of metal ions in RNA structure formation and folding stability, which is important for understanding RNA functions and the rational design of RNA structures.

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“…As both domains showed simultaneous binding to SL7 14merLoop RNA as confirmed by chemical shift perturbations in both domains upon SL7 14merLoop titration and filter binding experiments, we can conclude that both domains in the tandem construct bind to this RNA. Binding of two tandem dsRBD domains to short sequences similar to SL7 14merLoop have been shown before for nuclear factor 90 (NF90) dsRBDs wherein the two domains bind on either side of the short 18mer duplex RNA and show a binding stoichiometry of 1:2 RNA to protein (59). Therefore, dsRBD1,2 could indeed be accommodated on either side of the double stranded SL7 14merLoop RNA and as there is no free RNA surface remaining for further interactions with either dsRBDs, this could prevent sliding of the dsRBD1,2 on the SL7 14merLoop as observed in our NMR experiments.…”

Section: Discussionmentioning

confidence: 74%

Structure, dynamics and roX2-lncRNA binding of tandem double-stranded RNA binding domains dsRBD1,2 of Drosophila helicase Maleless

Jagtap¹,

Müller

Masiewicz³

et al. 2018

Preprint

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Maleless (MLE) is an evolutionary conserved member of the DExH family of helicases in Drosophila.Besides its function in RNA editing and presumably siRNA processing, MLE is best known for its role in remodelling non-coding roX RNA in the context of X chromosome dosage compensation in male flies.MLE and its human orthologue, DHX9 contain two tandem double-stranded RNA binding domains (dsRBDs) located at the N-terminal region. The two dsRBDs are essential for localization of MLE at the X-territory and it is presumed that this involves binding roX secondary structures. However, for dsRBD1 roX RNA binding has so far not been described. Here, we determined the solution NMR structure of dsRBD1 and dsRBD2 of MLE in tandem and investigated its role in double-stranded RNA (dsRNA) binding. Our NMR data show that both dsRBDs act as independent structural modules in solution and are canonical, non-sequence-specific dsRBDs featuring non-canonical KKxAK RNA binding motifs.NMR titrations combined with filter binding experiments document the contribution of dsRBD1 to dsRNA binding in vitro. Curiously, dsRBD1 mutants in which dsRNA binding in vitro is strongly compromised do not affect roX2 RNA binding and MLE localization in cells. These data suggest alternative functions for dsRBD1 in vivo.

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Nuclear factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA

Cited by 41 publications

References 51 publications

Structural basis of si RNA recognition by TRBP double‐stranded RNA binding domains

Structural basis of si RNA recognition by TRBP double‐stranded RNA binding domains

MCTBI: a web server for predicting metal ion effects in RNA structures

Structure, dynamics and roX2-lncRNA binding of tandem double-stranded RNA binding domains dsRBD1,2 of Drosophila helicase Maleless

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