ADAT2/3-mediated tRNA editing promotes cancer cell growth and tumorigenicity

Adenosine to Inosine (A-to-I) editing in the tRNA anticodon at position A34 is an important modification that expands anticodon-codon recognition at the wobble position and is required for normal mRNA translation. The relevance of tRNA editing in cancer remains unexplored.

Here we find that decreased tRNA editing upon ADAT2 depletion leads to defective translation of a subset of mRNAs. Thus, ADATmediated tRNA modification promotes oncogenesis by enhancing the translation of growth promoting mRNAs that are enriched in NNC codons that lack cognate tRNAs and therefore depend on A-I tRNA editing for decoding and mRNA translation.