Background
To better understand about ARS related rare disease, here are some terms related. All the details are based on MAMITLO message in Cutoperia Telegram group message and Ethan Pipeline lab meeting slide deck.
ARS
ARS = Aminoacyl-tRNA Synthetase
An enzyme that help to build protein by connecting amino acids to the correct tRNAs. - MAMITLO
Further self-study of 5 mins Youtube on tRNA charging about how the charged tRNA connecting amino acids.
ARSs
ARS/ARSs is used when referring broadly to this entire family of enzymes. - MAMITLO
Below is the ARSs family
AARS
AARS = Alanyl Aminoacyl-tRNA Synthetase
AARS = the gene that encodes Alanyl-tRNA synthetase — one member of the ARS family. - MAMITLO
AARS1 & AARS2
AARS1: the cytoplasmic version (works in the cell body)
AARS2: the mitochondrial version (works in the mitochondria)
| Feature | AARS1 | AARS2 |
|---|---|---|
| Location | Cytoplasm (main cell body) | Mitochondria (cell's energy factory) |
| Gene Name | AARS1 | AARS2 |
| Protein Product | Alanyl-tRNA synthetase, cytoplasmic | Alanyl-tRNA synthetase 2, mitochondrial |
| Function | Charges tRNA^Ala for cytoplasmic protein synthesis | Charges mitochondrial tRNA^Ala for mitochondrial protein synthesis |
| Pathways Involved | General protein translation | Mitochondrial translation (13 key proteins) |
| Associated Disorders | Some forms of Charcot-Marie-Tooth disease, leukodystrophy | Can cause mitochondrial diseases, such as infantile-onset cardiomyopathy, leukoencephalopathy, or combined oxidative phosphorylation deficiency |
AARS2 deficiency
one of 1,500+ inherited metabolic diseases that currently have no approved treatments. - Curetopia
Mutations in ARS genes have been implicated in various diseases, including neuropathies, encephalopathies, and other rare genetic disorders. These diseases, often early-onset and multisystemic, lack effective treatments, highlighting the urgent need for innovative therapeutic strategies. - Curetopia
AARS2 deficiency is linked to fatal infantile hypertrophic mitochondrial cardiomyopathy and Progressive Leukoencephalopathy With Ovarian Failure. - Curetopia
