CMTr cap-adjacent 2′-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses

Haussmann, Irmgard U. and Wu, Yanying and Nallasivan, Mohanakarthik P. and Archer, Nathan and Bodi, Zsuzsanna and Hebenstreit, Daniel and Waddell, Scott and Fray, Rupert and Soller, Matthias (2022) CMTr cap-adjacent 2′-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses. Nature Communications, 13 (1). ISSN 2041-1723

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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.

Item Type: Article
Identification Number: https://doi.org/10.1038/s41467-022-28549-5
Dates:
DateEvent
18 January 2022Accepted
8 March 2022Published Online
Subjects: CAH03 - biological and sport sciences > CAH03-01 - biosciences > CAH03-01-02 - biology (non-specific)
CAH03 - biological and sport sciences > CAH03-01 - biosciences > CAH03-01-08 - molecular biology, biophysics and biochemistry
Divisions: Faculty of Health, Education and Life Sciences > Centre for Life and Sport Sciences (C-LASS)
Depositing User: Irmgard Haussmann
Date Deposited: 21 Mar 2022 11:19
Last Modified: 21 Mar 2022 11:19
URI: http://www.open-access.bcu.ac.uk/id/eprint/12960

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