Lysyl-tRNA synthetase (LysRS) is an essential enzyme in the process of protein synthesis. It belongs to the family of aminoacyl-tRNA synthetases (aaRSs), which are responsible for attaching amino acids to their corresponding tRNAs, a process known as tRNA aminoacylation or tRNA charging. This enzyme specifically catalyzes the attachment of lysine to its cognate tRNA, forming lysyl-tRNA, which is then used in the ribosome for protein synthesis.
Human LysRS is a component of the multi-tRNA synthetase complex (MSC), which includes several other aaRSs and non-enzyme proteins. The MSC is crucial not only for protein translation but also for various cellular pathways such as immune response and cell migration . The structure of LysRS is dynamic and can be stabilized by forming complexes with other proteins, such as aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This interaction helps maintain the enzyme’s activity under stressed conditions .
The evolutionary emergence of the MSC in metazoans, including humans, is believed to protect the aminoacyl-tRNA synthetase components from being modified or recruited for other cellular pathways . This complex formation is less common in single-celled organisms, where LysRS and other aaRSs typically function independently.
LysRS has been implicated in various diseases, including cancer. For instance, the enzyme’s activity is significantly upregulated in hepatocellular carcinoma (HCC) tumor tissues compared to tumor-free liver tissues . This upregulation is associated with worse patient survival and higher tumor recurrence, making LysRS a potential therapeutic target in liver cancer .