Epitranscriptomic m6A regulation following spinal cord injury

Abstract

RNA methylation is involved in multiple physiological and pathological processes. However, the role of RNA methylation in spinal cord regeneration has not been reported. In this study, we find an altered m6A (N6-methyladenosine) RNA methylation profiling following zebrafish spinal cord injury (SCI), in line with an altered transcription level of the m6A methylase Mettl3. Interestingly, many of the differential m6A-tagged genes associated with neural regeneration are hypomethylated, but their transcription levels are upregulated in SCI. Moreover, we find that METTL3 may be important for spinal cord regeneration. We also show a conserved feature of METTL3 changes in mouse SCI model, in which the expression of METTL3 is increased in both astrocytes and neural stem cells. Together, our results indicate that m6A RNA methylation is dynamic and conserved following SCI and may contribute to spinal cord regeneration.

N6-Methyladenosine RNA Modification: A Potential Regulator of Stem Cell Proliferation and Differentiation

“…In adult mNSCs, Mettl3 depletion suppressed neuronal development, and skewed the NSCs to differentiate more toward glial lineage by modulating histone methyltransferase Ezh2 and the consequent H3K27me3 levels (Chen J et al, 2019). In zebrafish spinal cord injury model, the m 6 A RNA methylation profiling and transcription level of METTL3 were both increased, which is consistent with the results observed in NSCs in mice with spinal cord injury, indicating METTL3 may contribute to the spinal cord regeneration ( Xing et al, 2021 ).…”

METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury

“…The SRAMP database predicted that EEF1A2 might be modified by m6A methylation. Previous studies have noted that m6A RNA methylation profiling was altered in SCI [ 36 ]. METTL14 is upregulated in human and rat calcified arteries [ 37 ].…”

Epitranscriptomic signatures in stem cell differentiation to the neuronal lineage

“…In the case of CNS, even though it is most likely that regeneration will not occur following a lesion, one study has offered new insights regarding spinal cord injuries (SCI). Xing et al [ 87 ] have demonstrated for the first time, that following SCI most regeneration-related genes are highly m 6 A methylated. Also, they have found an increase in the expression level of METTL3 in both zebra fish and mice following SCI, demonstrating that the regeneration process is at least partly regulated by epitranscriptomic modifications.…”