Investigating the role of m6A RNA methylation in stem cell regulation and regeneration in the model flatworm Macrostomum lignano

- m6A methylation is one of the most common and conserved RNA modification primarily found in mRNAs. It is involved in important processes regarding cellular proliferation and differentiation such as development, regeneration and stem cell regulation. Recent studies have discovered that in the planarian flatworm model Schmidtea mediterranea, which is able of whole-body regeneration, the knock-down of some m6A machinery genes prevents regeneration after amputation, suggesting how this epitranscriptomic modification is fundamental for regeneration. Here, I present a study where we investigated the role of m6A methylation machinery proteins in regulating the activity of somatic stem cells called neoblasts, in another free-living flatworm model Macrostomum lignano. Starting from previous data, we explored this mechanism through experiments of RNA interference (RNAi) and In Situ Hybridization (ISH), on genes expressing major conserved components of m6A machinery during regeneration at different life stages of the worms. Results showed impaired neoblasts homoeostasis activity in adults and hindered regeneration in amputated worms, showing the importance of stem cells epitranscriptomics in the regulation of neoblasts. Moreover, A far less penetrant phenotype was observed in the treatment with hatchlings and not significant results were found by treating eggs. Overall, these experiments offer new insights into the role of m6A machinery in M. lignano’s neoblast activity, which understanding would significantly impact research on ageing and regeneration.