{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DARS1 encodes the cytoplasmic aspartyl‐tRNA synthetase, an enzyme essential for protein biosynthesis through catalysis of the attachment of aspartate to its cognate tRNA. In its canonical role, DARS1 ensures the fidelity of translation across all cell types. However, studies have revealed that mutations in DARS1 give rise to a distinct leukodystrophy—hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL)—highlighting its critical importance for white matter integrity and neural development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In mouse models, DARS1 is expressed ubiquitously but displays a particularly distinct pattern in the brain, with enrichment in neuronal somata and along neurites, suggesting an additional role in local protein synthesis at synapses; notably, complete loss of DARS1 function is embryonically lethal, emphasizing its indispensable cellular functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, in the context of cancer biology, the long non‐coding RNA DARS‐AS1 has been shown to upregulate the nearby DARS gene by sequestering miR‑194‑5p, thereby driving oncogenic processes in clear cell renal cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Collectively, these findings illustrate that DARS1 is not only fundamental for accurate protein translation but also plays critical roles in neural development and maintenance—with its disruption leading to severe neurological disease—and, when aberrantly activated, may contribute to tumor progression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ryan J Taft, Adeline Vanderver, Richard J Leventer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2013.04.006"}], "href": "https://doi.org/10.1016/j.ajhg.2013.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23643384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23643384"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nicole I Wolf, Camilo Toro, Ilya Kister, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000001157"}], "href": "https://doi.org/10.1212/WNL.0000000000001157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25527264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25527264"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dominik Fröhlich, Alexandra K Suchowerska, Ziggy H T Spencer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vivocharacterization of the aspartyl-tRNA synthetase DARS: Homing in on the leukodystrophy HBSL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2016.10.008"}], "href": "https://doi.org/10.1016/j.nbd.2016.10.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27816769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27816769"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Min Jiao, Hui Guo, Yule Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DARS-AS1 promotes clear cell renal cell carcinoma by sequestering miR-194-5p to up-regulate DARS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2020.110323"}], "href": "https://doi.org/10.1016/j.biopha.2020.110323"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32526457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32526457"}]}]}]}