FMRP Interacts with C/D Box snoRNA in the Nucleus and Regulates Ribosomal RNA Methylation
FMRP Interacts with C/D Box snoRNA in the Nucleus and Regulates Ribosomal RNA Methylation
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DOI：
10.1016/j.isci.2018.11.007
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发表时间：
2018-11-30
期刊：
影响因子：
5.8
通讯作者：
Muddashetty, Ravi S.
中科院分区：
文献类型：
--
作者：
D'Souza, Michelle Ninochka;Gowda, Naveen Kumar Chandappa;Muddashetty, Ravi S.
FMRP是一种RNA结合蛋白，已知定位于细胞质和细胞核中。在这里，我们已经确定了FMRP与细胞核中一组特定的C/D盒snoRNA的相互作用。C/D盒snoRNA引导核糖体RNA（rRNA）在限定位点上的2 'O甲基化，并且这种修饰调节rRNA折叠和核糖体组装。在人胚胎干细胞中，rRNA的2 'O甲基化在几个位点上是部分的，这导致核糖体具有不同的甲基化模式。FMRP-snoRNA相互作用影响这些位点中的几个上的rRNA甲基化，并且在不存在FMRP的情况下，rRNA的差异甲基化模式显著改变。我们发现，FMRP识别的核糖体上携带特定的甲基化模式的rRNA和甲基化模式的FMRP的识别可能会决定其靶mRNA的翻译状态。因此，FMRP将其功能整合在细胞核和细胞质中。
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.