The m5C reader protein Ybx1 promotes axon growth by regulating local translation in axons

It has been shown that 5-methylcytosine (m5C), one of the most abundant modifications on RNA, regulates various biological processes. However, the function of m5C modification in the nervous system is still largely unknown. Here, we show that the m5C reader Ybx1 is highly expressed in the developing mouse hippocampus in the central nervous system (CNS). Conditional knockout of Ybx1 in the dentate gyrus (DG) decreases mossy fiber growth and affects short-term memory. In the peripheral nervous system (PNS), the mRNA of Ybx1 is enriched in the axons of dorsal root ganglion (DRG) neurons and can be locally translated. Inhibition of local translation of Ybx1 results in a decrease in axon growth. We further identify 28 target mRNAs of Ybx1 in DRG neurons, including Ttl and Mmp24. Axon-specific knockdown of Ttl and Mmp24 decreases axon growth rate both in DRG and DG. It could be a general mechanism that locally translated Ybx1 regulates axon growth by controlling local translation in both CNS and PNS.