Effect of m6A on neuronal mRNA translocation from soma to neurites in the developing brain

Neurons are highly polarized cells with extensive neuronal processes, including dendrites and axons. All the RNA required by neurons is synthesized in the soma, while distinct neurites still require various RNAs. The soma and neurites contain different transcriptomes tailored to their specialized functions. m6A modification, the most abundant RNA modification in eukaryotes, can affect RNA stability and translation efficiency. Here, we suggest that m6A also affects RNA translocation in neurons and can alter the transcriptome in distal neurites. To investigate this, we micro-dissected soma and axons from the corpus callosum of P0 mouse brains and conducted RNA-seq on both WT and Nestin-Cre Mettl14 conditional knockout mice. We found that m6A modification positively promotes the neurite localization of a subset of mRNAs related to axonogenesis and growth cone regulation, which is essential for normal axonogenesis. Overall design: To examine the functional contribution of m6A modification in developing axons, we conducted RNA-seq using microdissected tissue from the axon-enriched Corpus Callosum of cortical projection neurons (layer 2/3) at P4, a time-point at which the maximum number of axons are distally projected in the callosal region and remain in the white matter before entering the cortical plates.