Figure 4.
Dynamic tRNA methylation impacts tRF biogenesis and directs stem cell fate. (A) Nsun2 and Dnmt2-mediated m5C protects tRNAs from angiogenin cleavage. Low levels of NSUN2 in mouse and human epidermal stem cells lead to accumulation of tiRNAs that repress protein synthesis. Conversely, epidermal progenitors up-regulate Nsun2 to inhibit angiogenic-mediated tRNA cleavage and promote epidermal differentiation. (B) Nsun2-depletion leads to neurological disorders caused by accumulation of stress-induced tiRNAs in vivo. Nsun2-deficient neuronal cells display increased stress granules assembly, reduced size and impaired maturation. These defects are specifically rescued by angiogenin inhibition that reduces tiRNA levels in these cells.