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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DOI：
10.1038/s41467-022-28549-5
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发表时间：
2022-03-08
影响因子：
16.6
通讯作者：
Soller M
中科院分区：
文献类型：
--
作者：
Haussmann IU;Wu Y;Nallasivan MP;Archer N;Bodi Z;Hebenstreit D;Waddell S;Fray R;Soller M
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（cOMe）处被O-甲基化。然而，cOMe在动物中的功能在很大程度上仍然未知。在这里，我们表明，两个帽甲基转移酶（CMTr 1和CMTr 2）的果蝇可以甲基化的核糖的第一个核苷酸的mRNA。双突变果蝇缺乏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中的条件表达来挽救。CMTr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是将未翻译的mRNA定位于突触所必需的，并增强帽结合复合物在细胞核中的结合。因此，我们的研究揭示了一种机制，共转录启动mRNAs的cOMe的本地化的蛋白质合成在突触。果蝇信使RNA中的两个帽甲基转移酶（CMTrs）使第一个帽相邻核苷酸的核糖冗余甲基化。在这里，CMTR是奖赏学习和将未翻译的信使RNA定位到突触所必需的。
Cap-adjacent nucleotides of animal, protist and viral mRNAs can be O-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) of Drosophila can 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. The two cap methyltransferases (CMTrs) redundantly methylate riboses of first cap adjacent nucleotides in messenger RNAs in Drosophila. Here, CMTrs are required for reward learning and localization of untranslated messenger RNAs to synapses.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Cheng, YZ;Endo, K;Davis, RL
通讯作者：
Davis, RL
影响因子：
8.8
作者：
Fritzsche, Renate;Karra, Daniela;Kiebler, Michael A.
通讯作者：
Kiebler, Michael A.
DOI：
10.1073/pnas.72.5.1904
发表时间：
1975-01-01
影响因子：
11.1
作者：
FURUICHI, Y;MORGAN, M;DARNELL, JE
通讯作者：
DARNELL, JE
影响因子：
64.5
作者：
Darnell JC;Van Driesche SJ;Zhang C;Hung KY;Mele A;Fraser CE;Stone EF;Chen C;Fak JJ;Chi SW;Licatalosi DD;Richter JD;Darnell RB
通讯作者：
Darnell RB