Translation Initiation from Two In-Frame AUGs Generates Mitochondrial and Cytoplasmic Forms of the p43 Component of the Multisynthetase Complex

Abstract

In humans, nine aminoacyl-tRNA synthetases form a stable multiprotein complex with the three auxiliary proteins p18, p38, and p43. The N-terminal moiety of p43 is involved in its anchoring to the complex, and its C-terminal moiety has a potent tRNA binding capacity. The p43 component of the complex is also the precursor of p43(ARF), an apoptosis-released factor, and of p43(EMAPII), the endothelial-monocyte activating polypeptide II. Here we identified a new translation product of the gene of p43, which contains nine additional N-terminal amino acid residues. This gene product is targeted to the mitochondria and accounts for 2% of p43 expressed in human cells. The cytoplasmic and mitochondrial species of p43 are produced from the same mRNA by a mechanism of leaky scanning of the AUG codon at position -27, which is in an unfavorable sequence context for translation initiation. The finding that a mitochondrial species of p43 exists in human cells further exemplifies the multifaceted implications of p43 and opens new perspectives for the understanding of the role of p43 in the apoptotic cell.