CMTr cap-adjacent 2'- O -ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses
CMTr cap-adjacent 2'- O -ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses
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CMTr 帽相邻的 2-O-核糖 mRNA 甲基转移酶是奖励学习和 mRNA 定位到突触所必需的
DOI：
10.1101/2021.06.24.449724
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Haussmann I
中科院分区：
文献类型：
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作者：
Haussmann I
动物、原生生物和病毒mrna的帽邻近核苷酸可以在核糖的2 '位置被o -甲基化（cOMe）。然而，cOMe在动物体内的功能在很大程度上仍然未知。在这里，我们发现果蝇的两个帽甲基转移酶（CMTr1和CMTr2）甲基化mRNA中第一个核苷酸的核糖。双突变蝇缺乏cOMe，但可以存活。与突出的神经元表达一致，它们具有奖励学习缺陷，可以通过训练前蘑菇体神经元的条件表达来拯救。CMTr的靶点包括细胞粘附和信号分子。许多与学习有关，也是脆性X智力迟钝蛋白（FMRP）的目标。与FMRP一样，cOMe是将非翻译mrna定位到突触所必需的，并增强了细胞核中帽结合复合物的结合。因此，我们的研究揭示了一种机制，通过cOMe共同转录启动mrna，用于突触的局部蛋白质合成。
Cap-adjacent nucleotides of animal, protist and viral mRNAs can beO-methylated at the 2‘ position of the ribose (cOMe). The functions of cOMe in animals, however, remain largely unknown. Here we show that the two cap methyltransferases (CMTr1 and CMTr2) ofDrosophilacan methylate the ribose of the first nucleotide in mRNA. Double-mutant flies lack cOMe but are viable. Consistent with prominent neuronal expression, they have a reward learning defect that can be rescued by conditional expression in mushroom body neurons before training. Among CMTr targets are cell adhesion and signaling molecules. Many are relevant for learning, and are also targets of Fragile X Mental Retardation Protein (FMRP). Like FMRP, cOMe is required for localization of untranslated mRNAs to synapses and enhances binding of the cap binding complex in the nucleus. Hence, our study reveals a mechanism to co-transcriptionally prime mRNAs by cOMe for localized protein synthesis at synapses.