Location alters tRNA identity: Trypanosoma brucei's cytosolic elongator tRNA Met is both the initiator and elongator in mitochondria

As a rule, protein synthesis is initiated with methionine or formyl methionine from the first AUG codon in an ORF and that AUG is recognized by an initiator tRNAMet-i. Internal AUG codons are then translated by a second tRNA, the elongator tRNAMet-e (1). In eubacteria, mitochondria, and chloroplasts, the tRNAMet-i is charged with methionine, and subsequently the methionine is formylated by a methionyl-tRNA transformylase, whereas in the eukaryotic cytosol and archea, the methionine on the tRNAMet-i is not formylated (2). Until now, the one known exception to the tRNAMet-i/tRNAMet-e paradigm occurred in animal mitochondria where a single mtDNA-coded tRNA is thought to serve for both initiation and elongation (3). The work of Tan et al. (4) in this issue of PNAS provides a second exception with several different twists as they show that the function of a tRNA in initiation and/or elongation depends on its location. Although all mtDNAs code for rRNAs necessary to support mitochondrial protein synthesis, the number of tRNAs coded by mtDNA varies widely. Some mtDNAs code for a complete set of tRNAs needed for protein synthesis, and some have an incomplete set and depend on import of certain cytosolic tRNAs (5). Still others do not contain any tRNA genes and must import a full complement of tRNAs from the cytosol. Trypanosoma brucei belongs to the latter class of organisms, and when Tan et al. (4) analyzed its nearly complete genome sequence (supplied by The Institute for Genomic Research (Rockville, MD) and the Sanger Institute (Cambridge, U.K.) for methionine tRNA genes, as expected, they found genes coding for distinct initiator-like and elongator-like tRNAs. One has an A1:U72 base pair and three consecutive GC base pairs at the end of the anticodon stem, A54 and A60, and lacks the TΨC …