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CMTr cap-adjacent 2`-O-ribose mRNA methyltransferases are required for reward learning

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Haussmann, Irmgard U., Wu, Yanying, Nallasivan, Mohanakarthik P., Archer, Nathan, Bodi, Zsuzsanna, Hebenstreit, Daniel, Waddell, Scott, Fray, Rupert and Soller, Matthias (2022) CMTr cap-adjacent 2`-O-ribose mRNA methyltransferases are required for reward learning. Nature Communications, 13 . 1209. doi:10.1038/s41467-022-28549-5 ISSN 2041-1723.

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Official URL: https://doi.org/10.1038/s41467-022-28549-5

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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: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Messenger RNA, Gene expression, Nucleotides , Ribose
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group
ISSN: 2041-1723
Official Date: 8 March 2022
Dates:
DateEvent
8 March 2022Available
18 January 2022Accepted
Volume: 13
Article Number: 1209
DOI: 10.1038/s41467-022-28549-5
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 19 January 2022
Date of first compliant Open Access: 13 April 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/R002932/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDLeverhulme Trusthttp://dx.doi.org/10.13039/501100000275
BB/R001715/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/M017982/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/M017982/1 [EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
BB/L006340/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
200846/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
789274European Research Councilhttp://dx.doi.org/10.13039/501100000781
UNSPECIFIEDUniversity Of Nottinghamhttp://dx.doi.org/10.13039/501100000837
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