Depletion of Mettl3 in cholinergic neurons causes adult-onset neuromuscular degeneration.

ABSTRACT: 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 (m⁶A) is a post-transcriptional RNA modification that controls diverse aspects of RNA metabolism. To assess the m⁶A requirement in MNs, we depleted the m⁶A 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. Mice with cholinergic neuron-specific METTL3 depletion display a progressive decline in motor behavior, accompanied by MN loss and muscle denerv

SUBMITTER: Dermentzaki G 

PROVIDER: S-EPMC11216409 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature