RGG-box in hnRNPA1 specifically recognizes the telomere G-quadruplex DNA and enhances the G-quadruplex unfolding ability of UP1 domain

Ghosh, Meenakshi and Singh, Mahavir (2018) RGG-box in hnRNPA1 specifically recognizes the telomere G-quadruplex DNA and enhances the G-quadruplex unfolding ability of UP1 domain. In: NUCLEIC ACIDS RESEARCH, 46 (19). pp. 10246-10261.

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Abstract

hnRNPA1 is a member of heteronuclear ribonucleoproteins that has been shown to promote telomere elongation apart from its roles in RNA transport and alternative splicing. It is a modular protein with an N-terminal domain called UP1 that consists of two RNA Recognition Motifs (RRM1 and RRM2 domains) and a C-terminal region that harbors functional motifs such as RGG-box, a prion-like domain, and a nuclear shuttling sequence. UP1 has been reported to bind and destabilize telomeric DNA G-quadruplexes and thereby participate in DNA telomere remodeling. An RGG-box motif that consists of four RGG repeats (containing arginine and glycine residues) is located C-terminal to the UP1 domain and constitutes an additional nucleic acid and protein-binding domain. However, the precise role of the RGG-box of hnRNPA1 in telomere DNA recognition and G-quadruplex DNA unfolding remains unexplored. Here, we show that the isolated RGG-box interacts specifically with the structured telomere G-quadruplex DNA but not with the single-stranded DNA. Further the interaction of the RGG-box with the G-quadruplex DNA is dependent on the loop nucleotides of the G-quadruplex. Finally, we show that the RGG-box enhances the G-quadruplex unfolding activity of the adjacent UP1 domain. We propose that UP1 and RGG-box act synergistically to achieve complete telomere G-quadruplex DNA unfolding.

Item Type:	Journal Article
Publication:	NUCLEIC ACIDS RESEARCH
Publisher:	OXFORD UNIV PRESS
Additional Information:	copyright for this article belongs to OXFORD UNIV PRESS
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Date Deposited:	19 Dec 2018 13:51
Last Modified:	19 Dec 2018 13:51
URI:	http://eprints.iisc.ac.in/id/eprint/61237

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