tRNAs Marked with CCACCA Are Targeted for Degradation

Author Manuscript 2012 May 11The CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase] adds CCA to the 3′ ends of transfer RNAs (tRNAs), a critical step in tRNA biogenesis that generates the amino acid attachment site. We found that the CCA-adding enzyme plays a key role in tRNA quality control by selectively marking structurally unstable tRNAs and tRNA-like small RNAs for degradation. Instead of adding CCA to the 3′ ends of these transcripts, CCA-adding enzymes from all three kingdoms of life add CCACCA. In addition, hypomodified mature tRNAs are subjected to CCACCA addition as part of a rapid tRNA decay pathway in vivo. We conjecture that CCACCA addition is a universal mechanism for controlling tRNA levels and preventing errors in translation.National Institutes of Health (U.S.) (Training Grant in Cellular, Biochemical and Molecular Sciences 5T32-GM068411)National Institutes of Health (U.S.) (Grant R01-GM34277)National Institutes of Health (U.S.) (Grant R01-CA133404)National Cancer Institute (U.S.) (Cancer Center Support (core) Grant P30-CA14051