Société Française de Biochimie et Biologie Moléculaire


IBPS,CNRS, INSERM, Sorbonne University

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

Life Science Alliance 2023 Jan 31; 6(4):e202201877. M, Dimitrova DG, Pigeon J, Paolantoni C, Ye T, Marchand V, Da Silva B, Schaefer E, Angelova MT, Stark Z, Delatycki M, Dudding-Byth T, Gecz J, Plaçais PY, Teysset L, Préat T, Piton A, Hassan BA, Roignant JY, Motorin Y, Carré C


Mira Brazane, 30 years old, is currently in the fourth year of her doctoral studies (funded by FRM, thesis defense scheduled for October 6, 2023) in the team 'Transgenerational Epigenetics and Small RNA Biology' led by Clément Carré and Laure Teysset. She holds a bachelor's and master's degree in microbiology from the University of Bejaia in Algeria, as well as a master's degree in biochemistry and molecular biology from Sorbonne University. Specializing in molecular biology and RNA biology, she has been supervised by Dr. Clément Carré since her second master's degree and currently during her Ph.D. Her thesis project focuses on the modification of transfer RNA by the methyltransferase FTSJ1. She has studied the biological functions of this modification, particularly in the regulation of gene expression by small regulatory RNAs and in protein synthesis, as well as its role in the etiology of intellectual disability associated with mutations in the FTSJ1 gene.


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Twitter : @MiraBrazane

Résumé de l'article

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.