Haissi Cui, Mridu Kapur, Jolene K Diedrich, John R Yates III, Susan L Ackerman, and Paul Schimmel
Nucleic Acids Research, gkaa1262, https://doi.org/10.1093/nar/gkaa1262
In mammalian cells, several aminoacyl tRNA synthetases (aaRS) form a multimeric complex, the MSC, and some version of this complex is conserved in eukaryotes and a subset of Archaea, suggesting a critical role. It has been assumed that multimerization facilitates efficient protein synthesis via proximity/mass-action effects, and collapse of the complex via deletion of its adaptors is lethal. However, it has remained unclear why some but not all aaRSs require this multimeric form. The authors use an elegant genetic approach to produce substantive evidence that ArgRS and GlRS have functions beyond their roles in protein synthesis. While the core idea is not new, the authors have engineered cells to lack the MSC-binding leucine zipper domain of ArgRS while retaining its tRNA catalytic activity and used them to provide compelling biochemical and cellular supporting evidence. An interesting finding is that expression of only the leucine zipper domain caused GlnRS to be retained in the MSC.