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Title: The RRM of the kRNA-editing protein TbRGG2 uses multiple surfaces to bind and remodel RNA

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gky1259· OSTI ID:1625573

Kinetoplastid RNA (kRNA) editing takes place in the mitochondria of kinetoplastid protists and creates translatable mRNAs by uridine insertion/deletion. Extensively edited (pan-edited) transcripts contain quadruplex forming guanine stretches, which must be remodeled to promote uridine insertion/deletion. Here we show that the RRM domain of the essential kRNA-editing factor TbRGG2 binds poly(G) and poly(U) RNA and can unfold both. A region C-terminal to the RRM mediates TbRGG2 dimerization, enhancing RNA binding. A RRM-U4 RNA structure reveals a unique RNA-binding mechanism in which the two RRMs of the dimer employ aromatic residues outside the canonical RRM RNA-binding motifs to encase and wrench open the RNA, while backbone atoms specify the uridine bases. Notably, poly(G) RNA is bound via a different binding surface. Thus, these data indicate that TbRGG2 RRM can bind and remodel several RNA substrates suggesting how it might play multiple roles in the kRNA editing process.

Research Organization:
Duke Univ., Durham, NC (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division
Grant/Contract Number:
AC02-05CH11231; P01GM0066275
OSTI ID:
1625573
Journal Information:
Nucleic Acids Research, Vol. 47, Issue 4; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 5 works
Citation information provided by
Web of Science

References (59)

The MRB1 complex functions in kinetoplastid RNA processing journal February 2009
The new (dis)order in RNA regulation journal April 2016
Structure of Propeller-Type Parallel-Stranded RNA G-Quadruplexes, Formed by Human Telomeric RNA Sequences in K + Solution journal February 2009
A three-dimensional working model for a guide RNA from Trypanosoma brucei journal June 1997
G-Quadruplex Formation by Human Telomeric Repeats-Containing RNA in Na + Solution journal August 2008
Uridine insertion/deletion editing in trypanosomes: a playground for RNA-guided information transfer: U-insertion/deletion editing in trypanosomes journal March 2011
Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition journal July 2013
Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA journal May 1999
Functional characterization of two paralogs that are novel RNA binding proteins influencing mitochondrial transcripts of Trypanosoma brucei journal August 2012
The RNA chaperone activity of the Trypanosoma brucei editosome raises the dynamic of bound pre-mRNAs journal January 2016
Recognition and Binding of Human Telomeric G-Quadruplex DNA by Unfolding Protein 1 journal May 2014
TbRGG1, an essential protein involved in kinetoplastid RNA metabolism that is associated with a novel multiprotein complex journal March 2008
The MURF3 gene of T. brucei contains multiple domains of extensive editing and is homologous to a subunit of NADH dehydrogenase journal September 1990
Structure of the Trypanosoma brucei p22 Protein, a Cytochrome Oxidase Subunit II-specific RNA-editing Accessory Factor journal April 2010
NMR structure of the three quasi RNA recognition motifs (qRRMs) of human hnRNP F and interaction studies with Bcl-x G-tract RNA: a novel mode of RNA recognition journal July 2006
Raver1 Interactions with Vinculin and RNA Suggest a Feed-Forward Pathway in Directing mRNA to Focal Adhesions journal June 2009
The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression: The RRM domain, a plastic RNA-binding platform journal April 2005
The Architecture of Trypanosoma brucei editosomes journal October 2016
Mitochondrial Complexes in Trypanosoma brucei: A Novel Complex and a Unique Oxidoreductase Complex journal December 2007
Dual core processing: MRB1 is an emerging kinetoplast RNA editing complex journal February 2013
Defining the RGG/RG Motif journal June 2013
Uridine insertion/deletion RNA editing in trypanosome mitochondria: A complex business journal March 2003
m1A and m1G disrupt A-RNA structure through the intrinsic instability of Hoogsteen base pairs journal August 2016
Developmental Cycles and Biology of Pathogenic Trypanosomes journal January 1985
U-Insertion/Deletion mRNA-Editing Holoenzyme: Definition in Sight journal February 2016
Crystal Structures of T. brucei MRP1/MRP2 Guide-RNA Binding Complex Reveal RNA Matchmaking Mechanism journal August 2006
Kinetoplastid phylogenetics, with special reference to the evolution of parasitic trypanosomes journal September 2008
Structures of the T. brucei kRNA editing factor MRB1590 reveal unique RNA-binding pore motif contained within an ABC-ATPase fold journal June 2015
Features and development of Coot journal March 2010
RRM–RNA recognition: NMR or crystallography…and new findings journal February 2013
Structural basis of G-tract recognition and encaging by hnRNP F quasi-RRMs journal June 2010
MRB3010 is a core component of the MRB1 complex that facilitates an early step of the kinetoplastid RNA editing process journal March 2011
Structural Basis for Telomerase RNA Recognition and RNP Assembly by the Holoenzyme La Family Protein p65 journal July 2012
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Guide RNA-Binding Complex from Mitochondria of Trypanosomatids journal October 2008
TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites journal September 2010
RBP16 is a multifunctional gene regulatory protein involved in editing and stabilization of specific mitochondrial mRNAs in Trypanosoma brucei journal April 2003
Structure of the RNA Binding Domain of a DEAD-Box Helicase Bound to Its Ribosomal RNA Target Reveals a Novel Mode of Recognition by an RNA Recognition Motif journal September 2010
Development and application of aromatic [13C, 1H] SOFAST-HMQC NMR experiment for nucleic acids journal September 2014
A Core MRB1 Complex Component Is Indispensable for RNA Editing in Insect and Human Infective Stages of Trypanosoma brucei journal October 2013
Trypanosome RNA Editing Mediator Complex proteins have distinct functions in gRNA utilization journal May 2017
Bacterial plasmid partition machinery: a minimalist approach to survival journal February 2012
Trypanosome RNA editing: the complexity of getting U in and taking U out: Trypanosome RNA editing journal November 2015
Architecture of the trypanosome RNA editing accessory complex, MRB1 journal March 2012
TbRGG2, an Essential RNA Editing Accessory Factor in Two Trypanosoma brucei Life Cycle Stages journal June 2008
The guide RNA database (3.0) journal January 1999
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Multiple G-quartet structures in pre-edited mRNAs suggest evolutionary driving force for RNA editing in trypanosomes journal July 2016
Adhesion Dance with Raver journal June 2009
STAT structure and function in signaling journal October 1998
Crystal Structure of the Human Nuclear Cap Binding Complex journal August 2001
RNA Interference Analyses Suggest a Transcript-specific Regulatory Role for Mitochondrial RNA-binding Proteins MRP1 and MRP2 in RNA Editing and Other RNA Processing in Trypanosoma brucei journal October 2004
Structure of hnRNP D Complexed with Single-stranded Telomere DNA and Unfolding of the Quadruplex by Heterogeneous Nuclear Ribonucleoprotein D journal February 2005
The OB-fold proteins of the Trypanosoma brucei editosome execute RNA-chaperone activity journal July 2018
Multifunctional G-Rich and RRM-Containing Domains of TbRGG2 Perform Separate yet Essential Functions in Trypanosome RNA Editing journal July 2012
RNA Binding and Core Complexes Constitute the U-Insertion/Deletion Editosome journal September 2014
Guide RNAs for transcripts with developmentally regulated RNA editing are present in both life cycle stages of Trypanosoma brucei. journal May 1992
Structure, properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery journal December 2016
PHENIX: a comprehensive Python-based system for macromolecular structure solution. text January 2010

Cited By (2)

MRB10130 is a RESC assembly factor that promotes kinetoplastid RNA editing initiation and progression journal June 2019
The La-related proteins: structures and interactions of a versatile superfamily of RNA-binding proteins journal December 2019

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