The 5' end of mature tRNAs is formed by the endonucleolytic removal of a leader sequence. RNase P, the enzyme generally responsible for this event, makes use of structural information contained within the tRNA domain of the precursor to recognize substrates and direct cleavage to the tRNA's 5' end. Human mitochondrial tRNA(Ser(AGY)GCU, a tRNA that , a tRNA that shows several structural deviations from "classical" as well as mitochondrial tRNAs, the most prominent of which is the lack of a D domain, is processed at its 5' end via a novel, "non-RNase P" pathway. 5' end maturation of tRNA(Ser(AGY)GCU is the consequence of 3' end processing of the abutting tRNA(His), precisely flanking the tRNA(Ser(AGY)GCU gene at its 5' end. Deletion of this adjoining tRNA structure abolishes efficient 5' end maturation of tRNA(Ser(AGY)GCU in vitro, suggesting that the human mitochondrial tRNA(SeR(AGY)GCU employs a 5'abutting tRNA as a processing signal for 5' end maturation in a kind of molecular commensalism.