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

In yeast, two aminoacyl-tRNA synthetases, MetRS and GluRS, are associated with Arc1p. We have studied the mechanism of this complex formation and found that the non-catalytic N-terminally appended domains of MetRS and GluRS are necessary and sufficient for binding to Arc1p. Similarly, it is the N-terminal domain of Arc1p that contains distinct but overlapping binding sites for MetRS and GluRS. Localization of Arc1p, MetRS and GluRS in living cells using green fluorescent protein showed that these three proteins are cytoplasmic 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 also a means of segregating the tRNA- aminoacylation machinery mainly to the cytoplasmic compartment.