Structural basis underlying CAC RNA recognition by the RRM domain of dimeric RNA-binding protein RBPMS

Quarterly Reviews of Biophysics
Marianna TeplovaDinshaw J Patel

Abstract

RNA-binding protein with multiple splicing (designated RBPMS) is a higher vertebrate mRNA-binding protein containing a single RNA recognition motif (RRM). RBPMS has been shown to be involved in mRNA transport, localization and stability, with key roles in axon guidance, smooth muscle plasticity, as well as regulation of cancer cell proliferation and migration. We report on structure-function studies of the RRM domain of RBPMS bound to a CAC-containing single-stranded RNA. These results provide insights into potential topologies of complexes formed by the RBPMS RRM domain and the tandem CAC repeat binding sites as detected by photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation. These studies establish that the RRM domain of RBPMS forms a symmetrical dimer in the free state, with each monomer binding sequence-specifically to all three nucleotides of a CAC segment in the RNA bound state. Structure-guided mutations within the dimerization and RNA-binding interfaces of RBPMS RRM on RNA complex formation resulted in both disruption of dimerization and a decrease in RNA-binding affinity as observed by size exclusion chromatography and isothermal titration calorimetry. As anticipated from biochemical binding s...Continue Reading

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Citations

Feb 6, 2019·Proceedings of the National Academy of Sciences of the United States of America·Nina RipinFrédéric H-T Allain
Jul 6, 2018·PLoS Genetics·Odelya H KaufmanFlorence L Marlow
May 7, 2020·Physical Chemistry Chemical Physics : PCCP·Casper de Lichtenberg, Johannes Messinger
Jul 26, 2018·PeerJ·Humberto FernandesMartyna Nowacka
Sep 7, 2018·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Matthew TorreSanda Alexandrescu
Nov 21, 2018·Expert Opinion on Drug Discovery·Xiao-Huan LiuMian-Bin Wu
Aug 11, 2019·Pediatric Cardiology·Alexander A AkerbergC Geoffrey Burns
Oct 9, 2020·Cold Spring Harbor Molecular Case Studies·Ajay GuptaBhuvana A Setty
Jun 10, 2021·Cell Death & Disease·Adriana MarceloClévio Nóbrega
Aug 21, 2021·Genes & Development·Cecilia Perez-BorrajeroSebastian Falk
Jul 13, 2021·Journal of Bacteriology·Amanda N D AdamsCarin K Vanderpool

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Methods Mentioned

BETA
immunoprecipitation
X-ray
PAR-CLIP
crosslinking studies
isothermal titration calorimetry
size exclusion chromatography
NMR

Software Mentioned

refine
PHASER
HKL2000
PHENIX
SHELEXD
AutoSol Wizard
CCP4 suite
Microcal ORIGIN

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