Georgia Dermentzaki, Mattia Furlan, Iris Tanaka, Tommaso Leonardi, Paola Rinchetti, Patricia M S Passos, Alliny Bastos, Yuna M Ayala, Jacob H Hanna, Serge Przedborski, Dario Bonanomi, Mattia Pelizzola, Francesco Lotti
Motor neuron (MN) demise is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Post-transcriptional gene regulation can control RNA's fate, and defects in RNA processing are critical determinants of MN degeneration. N6 -methyladenosine (m6 A) is a post-transcriptional RNA modification that controls diverse aspects of RNA metabolism. To assess the m6 A requirement in MNs, we depleted the m6 A methyltransferase-like 3 (METTL3) in cells and mice. METTL3 depletion in embryonic stem cell-derived MNs has profound and selective effects on survival and neurite outgrowth...
March 29, 2024: Cell Reports