The redundant protein synthesis gene Aimp1 challenges the canonical inverse relationship between translation and autophagy.

The fundamental processes of protein synthesis and autophagy are encoded by genes that vary in their essentiality for cellular fitness, and these genes are often inversely coupled through mTORC1 signaling. This study leverages analyses of gene essentiality genomic studies, to identify genes that are not only non-essential for cellular fitness, but also redundant for either protein synthesis or autophagy. This genomic approach identifies Aimp1, a highly conserved member of multi-aminoacyl tRNA synthetase complex thought to promote protein synthesis, Aimp1, as a limiter of autophagy in part through uncoupling of mTORC1 activity while minimally affecting protein synthesis. Transcriptomics analyses demonstrate that during immune responses protein synthesis and autophagy are inversely related. Depletion of Aimp1 in murine myeloid cells impairs innate immunity kinetics, thus unmasking an exemption in the inverse relationships between protein synthesis and autophagy. Our findings reveal that the functional redundancy of select protein synthesis genes, such as Aimp1, can reinforce autophagic activity, thereby challenging the canonical inverse relationship between translation and autophagy and highlighting a novel mechanism for maintaining cellular homeostasis.