The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance.

Details

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_39AAE65032F8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance.
Journal
Life science alliance
Author(s)
Brazane M., Dimitrova D.G., Pigeon J., Paolantoni C., Ye T., Marchand V., Da Silva B., Schaefer E., Angelova M.T., Stark Z., Delatycki M., Dudding-Byth T., Gecz J., Plaçais P.Y., Teysset L., Préat T., Piton A., Hassan B.A., Roignant J.Y., Motorin Y., Carré C.
ISSN
2575-1077 (Electronic)
ISSN-L
2575-1077
Publication state
Published
Issued date
04/2023
Peer-reviewed
Oui
Volume
6
Number
4
Pages
e202201877
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
FTSJ1 is a conserved human 2'-O-methyltransferase (Nm-MTase) that modifies several tRNAs at position 32 and the wobble position 34 in the anticodon loop. Its loss of function has been linked to X-linked intellectual disability (XLID), and more recently to cancers. However, the molecular mechanisms underlying these pathologies are currently unclear. Here, we report a novel FTSJ1 pathogenic variant from an X-linked intellectual disability patient. Using blood cells derived from this patient and other affected individuals carrying FTSJ1 mutations, we performed an unbiased and comprehensive RiboMethSeq analysis to map the ribose methylation on all human tRNAs and identify novel targets. In addition, we performed a transcriptome analysis in these cells and found that several genes previously associated with intellectual disability and cancers were deregulated. We also found changes in the miRNA population that suggest potential cross-regulation of some miRNAs with these key mRNA targets. Finally, we show that differentiation of FTSJ1-depleted human neural progenitor cells into neurons displays long and thin spine neurites compared with control cells. These defects are also observed in Drosophila and are associated with long-term memory deficits. Altogether, our study adds insight into FTSJ1 pathologies in humans and flies by the identification of novel FTSJ1 targets and the defect in neuron morphology.
Keywords
Humans, Methylation, Ribose, Intellectual Disability/genetics, Methyltransferases/genetics, RNA, Transfer/genetics, RNA, Transfer/metabolism, Neurons/metabolism, Nuclear Proteins/genetics
Pubmed
Web of science
Open Access
Yes
Create date
02/02/2023 14:15
Last modification date
20/04/2023 6:09
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