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

Nucleic Acids Research
Pravin Kumar Ankush JagtapJanosch Hennig

Abstract

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 and SAXS data show that both dsRBDs act as independent structural modules in solution and are canonical, non-sequence-specific dsRBDs featuring non-canonical KKxAXK RNA binding motifs. NMR titrations combined with filter binding experiments and isothermal titration calorimetry (ITC) 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 roX...Continue Reading

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Citations

Jun 9, 2020·Nucleic Acids Research·Marisa MüllerPeter B Becker
Dec 8, 2020·Journal of Biomolecular Structure & Dynamics·Renuka SuravajhalaPrashanth Suravajhala

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Datasets Mentioned

BETA
SASDF72

Methods Mentioned

BETA
nuclear magnetic resonance
size-exclusion
NMR
in vitro transcription
filter binding
saturation binding
X-ray
small-angle
immunoprecipitation
transfection

Software Mentioned

SL7
14merLoop
CCPN
ScÅtter
CellProfiler
NMRPipe
CYANA
ARIA
CCPNmr
SASBDB

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