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

被引:22
|
作者
D'Souza, Michelle Ninochka [1 ,4 ]
Gowda, Naveen Kumar Chandappa [1 ]
Tiwari, Vishal [1 ,2 ]
Babu, Rosana Ottakandathil [1 ]
Anand, Praveen [1 ]
Dastidar, Sudhriti Ghosh [1 ,5 ]
Singh, Randhir [1 ]
Selvaraja, Bhuvaneish [3 ]
Pal, Rakhi [1 ]
Ramesh, Arati [2 ]
Chattarji, Sumantra [1 ,2 ,3 ]
Chandran, Siddharthan [1 ,3 ]
Gulyani, Akash [1 ]
Palakodeti, Dasaradhi [1 ]
Muddashetty, Ravi S. [1 ]
机构
[1] Inst Stem Cell Biol & Regenerat Med, Bengaluru 560065, India
[2] Natl Ctr Biol Sci, Bengaluru 560065, Karnataka, India
[3] Univ Edinburgh, Ctr Neuroregenerat, Edinburgh EH16 4SB, Midlothian, Scotland
[4] Univ Transdisciplinary Hlth Sci & Technol TDU, Bengaluru 560064, Karnataka, India
[5] Manipal Acad Higher Educ, Manipal 576104, Karnataka, India
关键词
MENTAL-RETARDATION PROTEIN; FRAGILE-X-SYNDROME; MESSENGER-RNAS; TRANSLATION; REVEALS; RECEPTOR; 2-O-ME;
D O I
10.1016/j.isci.2018.11.007
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:399 / +
页数:35
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