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

Autor: Haussmann IU; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.; Department of Life Science, Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, B15 3TN, UK., Wu Y; Centre for Neuronal Circuits and Behaviour, The University of Oxford, Oxford, OX1 3TA, UK., Nallasivan MP; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK., Archer N; School of Veterinary Medicine and Sciences, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD, UK., Bodi Z; School of Biosciences, Plant Science Division, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD, UK., Hebenstreit D; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK., Waddell S; Centre for Neuronal Circuits and Behaviour, The University of Oxford, Oxford, OX1 3TA, UK., Fray R; School of Biosciences, Plant Science Division, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD, UK., Soller M; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. m.soller@bham.ac.uk.; Birmingham Centre for Genome Biology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. m.soller@bham.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Mar 08; Vol. 13 (1), pp. 1209. Date of Electronic Publication: 2022 Mar 08.
DOI: 10.1038/s41467-022-28549-5
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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