Published on March 18, 2019 in Nucleic Acids Res volume 47(5).

PubMed ID: 30541109

DOI: 5239036

Abstract:

Transfer RNA is heavily modified and plays a central role in protein synthesis andcellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m1A) and3-methylcytidine (m3C) demethylase of tRNA. ALKBH3 can promote cancer cellproliferation, migration and invasion. In vivo study confirms the regulation effectsof ALKBH3 on growth of tumor xenograft. The m1A demethylated tRNA is more sensitiveto angiogenin (ANG) cleavage, followed by generating tRNA-derived small RNAs (tDRs)around the anticodon regions. tDRs are conserved among species, which strengthen theribosome assembly and prevent apoptosis triggered by cytochrome c (Cyt c). Ourdiscovery opens a potential and novel paradigm of tRNA demethylase, which regulatesbiological functions via generation of tDRs.CI - © The Author(s) 2018. Published by Oxford University Press on behalf of NucleicAcids Research.