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G-quadruplex formation of oligonucleotides containing ALS and FTD related GGGGCC repeat

Content Provider	Springer Nature Link
Author	Brčić, Jasna Plavec, Janez
Copyright Year	2016
Abstract	A largely increased number of GGGGCC repeats located in the non-coding region of C9orf72 gene have been identified as the leading cause of two related neurological disorders, familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We examined G-quadruplex forming ability of GGGGCCrepeat containing oligonucleotides with four guanine tracts chosen as the smallest possible model to form a unimolecular G-quadruplex. These oligonucleotides are readily to folded into G-quadruplexes in the presence of K$^{+}$ ions. However, the formation of multiple structures makes structural analysis challenging and time consuming. We observed that flanking sequences on 5'- and 3'-ends as well as mutations of loop residues have a profound effect on folding. Sequence d[(G$_{4}$C$_{2}$)$_{3}$G$_{4}$] was chosen for further scrutiny and optimization of nuclear magnetic resonance (NMR) spectroscopic properties with dG to 8Br-dG substitutions at specific positions in the sequence under different folding conditions. Expectedly, folding into desired predominant topology is facilitated when substituted residue adopted a syn conformation in the naturally-occurring structure. Single dG to 8Br-dG substitution at position 21 and fine tuning of folding conditions facilitate folding of d[(G$_{4}$C$_{2}$)$_{3}$GG$^{Br}$GG] into (mostly) a single G-quadruplex, and thus enable determination of its high-resolution structure by high-field NMR.
Starting Page	222
Ending Page	237
Page Count	16
File Format	PDF
ISSN	20950179
Journal	Frontiers of Chemical Engineering in China
Volume Number	10
Issue Number	2
e-ISSN	20950187
Language	English
Publisher	Higher Education Press
Publisher Date	2016-02-01
Publisher Institution	Chinese Universities
Publisher Place	Beijing
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	G-quadruplex GGGGCC NMR ALS/FTD polymorphism Industrial Chemistry/Chemical Engineering Nanotechnology
Content Type	Text
Resource Type	Article
Subject	Chemical Engineering

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Solution structure of a DNA quadruplex containing ALS and FTD related GGGGCC repeat stabilized by 8-bromodeoxyguanosine substitution

Solution structure of a DNA quadruplex containing ALS and FTD related GGGGCC repeat stabilized by 8-bromodeoxyguanosine substitution

FUS regulates RAN translation through modulating the G-quadruplex structure of GGGGCC repeat RNA in C9orf72-linked ALS/FTD

Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs

Characterizations of distinct parallel and antiparallel G-quadruplexes formed by two-repeat ALS and FTD related GGGGCC sequence

Crystal structure of parallel G-quadruplex formed by the two-repeat ALS- and FTD-related GGGGCC sequence

Development of Therapeutics for C9ORF72 ALS/FTD-Related Disorders

The Disease-associated r(GGGGCC)n Repeat from the C9orf72 Gene Forms Tract Length-dependent Uni- and Multimolecular RNA G-quadruplex Structures

Molecular dynamics of the interaction between the ALS/FTD-associated (GGGGCC)n RNA G-quadruplex structure and the three RRM domains of hnRNP H

G-quadruplex formation of oligonucleotides containing ALS and FTD related GGGGCC repeat

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Solution structure of a DNA quadruplex containing ALS and FTD related GGGGCC repeat stabilized by 8-bromodeoxyguanosine substitution

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FUS regulates RAN translation through modulating the G-quadruplex structure of GGGGCC repeat RNA in C9orf72-linked ALS/FTD

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