FMRP Interacts with C/D Box snoRNA in the Nucleus and Regulates Ribosomal RNA Methylation
Michelle Ninochka D'Souza,
Naveen Kumar Chandappa Gowda,
Vishal Tiwari,
Rosana Ottakandathil Babu,
Praveen Anand,
Sudhriti Ghosh Dastidar,
Randhir Singh,
Owen G. James,
Bhuvaneish Selvaraj,
Rakhi Pal,
Arati Ramesh,
Sumantra Chattarji,
Siddharthan Chandran,
Akash Gulyani,
Dasaradhi Palakodeti,
Ravi S. Muddashetty
Affiliations
Michelle Ninochka D'Souza
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; The University of Trans-Disciplinary Health Sciences & Technology (TDU), Bengaluru, Karnataka 560064, India
Naveen Kumar Chandappa Gowda
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India
Vishal Tiwari
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; National Centre for Biological Sciences, Bengaluru, Karnataka 560065, India
Rosana Ottakandathil Babu
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India
Praveen Anand
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India
Sudhriti Ghosh Dastidar
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; Manipal Academy of Higher Education, Madhav Nagar, Manipal, Karnataka 576104, India
Randhir Singh
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India
Owen G. James
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK; UK Dementia Research Institute at Edinburgh, University of Edinburgh, Edinburgh EH16 4SB, UK
Bhuvaneish Selvaraj
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK; UK Dementia Research Institute at Edinburgh, University of Edinburgh, Edinburgh EH16 4SB, UK
Rakhi Pal
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India
Arati Ramesh
National Centre for Biological Sciences, Bengaluru, Karnataka 560065, India
Sumantra Chattarji
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; National Centre for Biological Sciences, Bengaluru, Karnataka 560065, India; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK
Siddharthan Chandran
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK; UK Dementia Research Institute at Edinburgh, University of Edinburgh, Edinburgh EH16 4SB, UK
Akash Gulyani
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India
Dasaradhi Palakodeti
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India
Ravi S. Muddashetty
Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru 560065, India; Corresponding author
Summary: 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. : Molecular Interaction; Stem Cells Research; Omics Subject Areas: Molecular Interaction, Stem Cells Research, Omics