RRC ID 70840
Author Haussmann IU, Wu Y, Nallasivan MP, Archer N, Bodi Z, Hebenstreit D, Waddell S, Fray R, Soller M.
Title CMTr cap-adjacent 2'-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses.
Journal Nat Commun
Abstract 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.
Volume 13(1)
Pages 1209
Published 2022-3-8
DOI 10.1038/s41467-022-28549-5
PII 10.1038/s41467-022-28549-5
PMID 35260552
PMC PMC8904806
MeSH Animals Fragile X Mental Retardation Protein / genetics Fragile X Mental Retardation Protein / metabolism Fragile X Syndrome* / genetics Methyltransferases* / genetics Methyltransferases* / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Reward Ribose / metabolism Synapses / metabolism
IF 12.121