Structure specific recognition of telomeric repeats containing RNA by the RGG-box of hnRNPA1

Nucleic Acids Research
Meenakshi Ghosh, Mahavir Singh

Abstract

The telomere repeats containing RNA (TERRA) is transcribed from the C-rich strand of telomere DNA and comprises of UUAGGG nucleotides repeats in humans. The TERRA RNA repeats can exist in single stranded, RNA-DNA hybrid and G-quadruplex forms in the cell. Interaction of TERRA RNA with hnRNPA1 has been proposed to play critical roles in maintenance of telomere DNA. hnRNPA1 contains an N-terminal UP1 domain followed by an RGG-box containing C-terminal region. RGG-motifs are emerging as key protein motifs that recognize the higher order nucleic acid structures as well as are known to promote liquid-liquid phase separation of proteins. In this study, we have shown that the RGG-box of hnRNPA1 specifically recognizes the TERRA RNA G-quadruplexes that have loops in their topology, whereas it does not interact with the single-stranded RNA. Our results show that the N-terminal UP1 domain in the presence of the RGG-box destabilizes the loop containing TERRA RNA G-quadruplex efficiently compared to the RNA G-quadruplex that lacks loops, suggesting that unfolding of G-quadruplex structures by UP1 is structure dependent. Furthermore, we have compared the telomere DNA and TERRA RNA G-quadruplex binding by the RGG-box of hnRNPA1 and discussed...Continue Reading

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Citations

Jun 20, 2020·Molecular Biology and Evolution·Elise PareyCamille Berthelot
Oct 2, 2020·Chemical Communications : Chem Comm·Tatsuki MasuzawaTakanori Oyoshi
Oct 12, 2021·Frontiers in Neuroscience·Myriam GagnéChristine Vande Velde

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Methods Mentioned

BETA
NMR
affinity purification
size exclusion chromatography
isothermal titration calorimetry
X-ray

Software Mentioned

NMRFAM
- SPARKY
ORIGIN

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