RT Journal Article SR Electronic T1 The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202201877 DO 10.26508/lsa.202201877 VO 6 IS 4 A1 Mira Brazane A1 Dilyana G Dimitrova A1 Julien Pigeon A1 Chiara Paolantoni A1 Tao Ye A1 Virginie Marchand A1 Bruno Da Silva A1 Elise Schaefer A1 Margarita T Angelova A1 Zornitza Stark A1 Martin Delatycki A1 Tracy Dudding-Byth A1 Jozef Gecz A1 Pierre-Yves Plaçais A1 Laure Teysset A1 Thomas Préat A1 Amélie Piton A1 Bassem A Hassan A1 Jean-Yves Roignant A1 Yuri Motorin A1 Clément Carré YR 2023 UL https://www.life-science-alliance.org/content/6/4/e202201877.abstract AB 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.