Arg-tRNA Synthetase Regulates SRRM2 Nuclear Condensate Trafficking and mRNA Maturation

Aminoacyl-tRNA synthetases (aaRSs) catalyze the first step in protein synthesis in the cytoplasm by charging amino acids to their cognate tRNAs. Prior work revealed the existence of nuclear-localized aaRSs that checked the ability of newly synthesized tRNAs to be charged before export to the cytoplasm. To explore other possible functions of nuclear aaRSs, we used co-immunoprecipitation and mass spectrometry to identify nuclear proteins that interact with arginyl-tRNA synthetase (ArgRS). We thus identified Serine/arginine repetitive matrix protein 2 (SRRM2), which assists in alignment of incipient splice junctions and is stored with multiple components of the RNA splicing apparatus in nuclear speckle condensates, as a strong interaction partner of ArgRS. Our analysis showed that ArgRS, which is a component of the multi-tRNA synthetase complex (MSC), co localized with SRRM2 in nuclear speckles. Using dynamic photo-bleaching experiments, we showed that, consistent with condensate properties, SRRM2 has a fluctuating appearance in speckles. shRNA knock down of ArgRS impeded SRRM2 speckle trafficking and, coincidently, altered splicing of pre-mRNA transcripts. Among the altered spliced variants, those of tRNA synthetase family members were among the most prominent. Thus, this work revealed an entirely new nuclear aaRS function that regulates nuclear condensate trafficking and RNA splicing, including of tRNA synthetase pre-mRNAs.