RARS (Arginyl-tRNA Synthetase) is an essential enzyme encoded by the RARS gene that catalyzes the attachment of arginine to its cognate tRNA. This aminoacyl-tRNA synthetase (aaRS) is critical for protein translation and is involved in various cellular processes beyond its canonical enzymatic function. Recent research has implicated RARS and related aaRS in neurodegenerative disease pathogenesis.
| Property | Value |
|---|---|
| Symbol | RARS |
| Full Name | Arginyl-tRNA Synthetase |
| Aliases | ArgRS |
| Chromosome | 5q31.3 |
| Gene ID | 10684 |
| Category | Translation/Protein Synthesis |
| Protein Class | Aminoacyl-tRNA synthetase |
RARS is a class I aminoacyl-tRNA synthetase that catalyzes the ATP-dependent attachment of L-arginine to the 3' end of tRNA^Arg. [1] The protein consists of:
Beyond translation, RARS participates in:
RARS is ubiquitously expressed with high levels in brain, particularly in neurons of the hippocampus and cerebral cortex. [5] This high expression in metabolically active neurons underscores its importance in neuronal protein homeostasis.
Mutations in multiple aminoacyl-tRNA synthetase genes, including RARS, have been implicated in ALS. [6] While RARS mutations are less common than those in other aaRS genes (like TARDBP and FUS), they contribute to the spectrum of translation-related ALS genes.
RARS variants have been associated with Charcot-Marie-Tooth (CMT) disease, a hereditary peripheral neuropathy. [7] These findings support the importance of translation machinery in peripheral nerve function.
While direct RARS mutations are not a major cause of AD/PD, several mechanisms suggest potential involvement:
Understanding RARS function in neurons may lead to therapeutic strategies:
Key questions remain:
Aminoacyl-tRNA synthetases: structure and function - Annu Rev Biochem. ↩︎
Leucine sensing by RARS in mTORC1 activation - Cell. 2014. ↩︎
RARS signaling functions beyond translation - J Mol Signal. ↩︎
Protein aggregation in neurodegeneration - Nat Rev Neurosci. ↩︎
Oxidative stress in neurodegeneration - Nat Rev Neurosci. ↩︎