The intracellular location of two animoacyl-tRNA synthetases depends on complex formation with Arc1p

In yeast, two aminoacyl-tRNA synthetases, MetRS and GluRS, are associated w ith Arc1p. We have studied the mechanism of this complex formation and foun d that the non-catalytic N-terminally appended domains of MetRS and GluRS a re necessary and sufficient for binding to Arc1p. Similarly, it is the N-te rminal domain of Arc1p that contains distinct but overlapping binding sites for MetRS and GluRS. Localization of Arc1p, MetRS and GluRS in living cell s using green fluorescent protein showed that these three proteins are cyto plasmic and largely excluded from the nucleus. However, when their assembly into a complex is inhibited, significant amounts of MetRS, GluRS and Arc1p can enter the nucleus. We suggest that the organization of aminoacyl-tRNA synthetases into a multimeric complex not only affects catalysis, but is al so a means of segregating the tRNA-aminoacylation machinery mainly to the c ytoplasmic compartment.