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iScience. 2018 Nov 7;9:399-411. doi: 10.1016/j.isci.2018.11.007. [Epub ahead of print]

FMRP Interacts with C/D Box snoRNA in the Nucleus and Regulates Ribosomal RNA Methylation.

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; The University of Trans-Disciplinary Health Sciences & Technology (TDU), Bengaluru, Karnataka 560064, India.
2
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India.
3
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; National Centre for Biological Sciences, Bengaluru, Karnataka 560065, India.
4
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; Manipal Academy of Higher Education, Madhav Nagar, Manipal, Karnataka 576104, India.
5
Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK.
6
National Centre for Biological Sciences, Bengaluru, Karnataka 560065, India.
7
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; National Centre for Biological Sciences, Bengaluru, Karnataka 560065, India; Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK.
8
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK.
9
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India. Electronic address: ravism@instem.res.in.

Abstract

FMRP is an RNA-binding protein that is known to localize in the cytoplasm and in the nucleus. Here, we have identified an interaction of FMRP with a specific set of C/D box snoRNAs in the nucleus. C/D box snoRNAs guide 2'O methylations of ribosomal RNA (rRNA) on defined sites, and this modification regulates rRNA folding and assembly of ribosomes. 2'O methylation of rRNA is partial on several sites in human embryonic stem cells, which results in ribosomes with differential methylation patterns. FMRP-snoRNA interaction affects rRNA methylation on several of these sites, and in the absence of FMRP, differential methylation pattern of rRNA is significantly altered. We found that FMRP recognizes ribosomes carrying specific methylation patterns on rRNA and the recognition of methylation pattern by FMRP may potentially determine the translation status of its target mRNAs. Thus, FMRP integrates its function in the nucleus and in the cytoplasm.

KEYWORDS:

Molecular Interaction; Omics; Stem Cells Research

PMID:
30469012
DOI:
10.1016/j.isci.2018.11.007
Free PMC Article

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