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

Author

Listed:
  • Irmgard U. Haussmann

    (University of Birmingham
    Birmingham City University)

  • Yanying Wu

    (The University of Oxford)

  • Mohanakarthik P. Nallasivan

    (University of Birmingham)

  • Nathan Archer

    (University of Nottingham)

  • Zsuzsanna Bodi

    (University of Nottingham)

  • Daniel Hebenstreit

    (University of Warwick)

  • Scott Waddell

    (The University of Oxford)

  • Rupert Fray

    (University of Nottingham)

  • Matthias Soller

    (University of Birmingham
    University of Birmingham)

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.

Suggested Citation

  • Irmgard U. Haussmann & Yanying Wu & Mohanakarthik P. Nallasivan & Nathan Archer & Zsuzsanna Bodi & Daniel Hebenstreit & Scott Waddell & Rupert Fray & Matthias Soller, 2022. "CMTr cap-adjacent 2′-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28549-5
    DOI: 10.1038/s41467-022-28549-5
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    References listed on IDEAS

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    1. Irmgard U. Haussmann & Zsuzsanna Bodi & Eugenio Sanchez-Moran & Nigel P. Mongan & Nathan Archer & Rupert G. Fray & Matthias Soller, 2016. "m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination," Nature, Nature, vol. 540(7632), pages 301-304, December.
    2. Michael S. Grotewiel & Christine D. O. Beck & Kwok Hang Wu & Xin-Ran Zhu & Ronald L. Davis, 1998. "Integrin-mediated short-term memory in Drosophila," Nature, Nature, vol. 391(6666), pages 455-460, January.
    3. James B. Brown & Nathan Boley & Robert Eisman & Gemma E. May & Marcus H. Stoiber & Michael O. Duff & Ben W. Booth & Jiayu Wen & Soo Park & Ana Maria Suzuki & Kenneth H. Wan & Charles Yu & Dayu Zhang &, 2014. "Diversity and dynamics of the Drosophila transcriptome," Nature, Nature, vol. 512(7515), pages 393-399, August.
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