The role of RNA modifications in regulation of planarian regeneration

Planarians are free-living flatworms that can regenerate using an abundant population of stem cells called neoblasts. Neoblasts are an important model for studying the cellular basis of regeneration, yet the regulation of neoblast gene expression remains poorly characterized. Post-transcriptional modifications to RNA have major roles in almost every aspect of mRNA metabolism. Using single cell RNA sequencing (scRNAseq), we found that genes encoding RNA-modifying genes are expressed specifically in neoblasts. Following differentiation, RNA-modifying gene expression declined by over 4-folds, indicating that RNA modifications in planarians have roles in neoblast-specific functions. Inhibition of genes that function in the RNA modification pathway by RNAi resulted in defects to tissue maintenance, activation of abnormal gene expression programs, and loss of regenerative abilities. However, these defects appeared without reduction in the number of neoblasts, suggesting that neoblast functions are affected and not neoblast viability. Moreover, despite the ubiquitous expression of RNA-modifying genes in neoblasts, differentiation defects appeared to be limited to several, but not all, cellular lineages.

Together, these results indicate that mRNA modifications are required for neoblasts to produce specific types of progeny cells committed to differentiation, and indicating that mRNA modifications have crucial roles in the control of tissue turnover and regeneration.