Aberrant methylation of tRNAs links cellular stress to neuro‐developmental disorders
Human diseases resulting from abnormal brain development like microcephaly are lifelong conditions that cannot be cured. Our study identifies neuronal cell death caused by cellular stress as one cause for microcephaly. The activation of cellular stress pathways leads to aberrant accumulation of small non-coding RNA fragments that derive from transfer RNAs (tRNAs). We prove the importance of this pathway by showing that specific small inhibitors blocking the cleavage of tRNAs can revert the delay in brain development. Thus, our study offers new therapeutic avenues of managing the disease symptoms to allow patients an optimal quality of life.
Full article in EMBO Journal
Blanco S, Dietmann S, Flores JV, Hussain S, Kutter C, Humphreys P, Lukk M, Lombard P, Treps L, Popis M, Kellner S, Hölter SM, Garrett L, Wurst W, Becker L, Klopstock T, Fuchs H, Gailus-Durner V, Hrabĕ de Angelis M, Káradóttir RT, Helm M, Ule J, Gleeson JG, Odom DT, Frye M. Aberrant methylation of tRNAs links cellular stress to neuro‐developmental disorders. EMBO Journal. PMID: 25063673.