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network","award":["ER-18-14-183"],"award-info":[{"award-number":["ER-18-14-183"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Histidyl-tRNA synthetase (HARS) ligates histidine to its cognate transfer RNA (tRNAHis). Mutations in HARS cause the human genetic disorders Usher syndrome type 3B (USH3B) and Charcot-Marie-Tooth syndrome type 2W (CMT2W). Treatment for these diseases remains symptomatic, and no disease specific treatments are currently available. Mutations in HARS can lead to destabilization of the enzyme, reduced aminoacylation, and decreased histidine incorporation into the proteome. Other mutations lead to a toxic gain-of-function and mistranslation of non-cognate amino acids in response to histidine codons, which can be rescued by histidine supplementation in vitro. We discuss recent advances in characterizing HARS mutations and potential applications of amino acid and tRNA therapy for future gene and allele specific therapy.<\/jats:p>","DOI":"10.3390\/genes14020254","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T03:16:52Z","timestamp":1674098212000},"page":"254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Towards a Cure for HARS Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Sarah D. P.","family":"Wilhelm","sequence":"first","affiliation":[{"name":"Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosan","family":"Kenana","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1961-9631","authenticated-orcid":false,"given":"Yi","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9500-8640","authenticated-orcid":false,"given":"Patrick","family":"O\u2019Donoghue","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada"},{"name":"Department of Chemistry, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilka U.","family":"Heinemann","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s41580-018-0011-4","article-title":"Roadblocks and resolutions in eukaryotic translation","volume":"19","author":"Schuller","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/anie.197106381","article-title":"Translation of genetic information on the ribosome","volume":"10","author":"Schreiber","year":"1971","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1146\/annurev.bi.54.070185.005333","article-title":"Eukaryotic protein synthesis","volume":"54","author":"Moldave","year":"1985","journal-title":"Annu. Rev. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1128\/MMBR.67.4.550-573.2003","article-title":"On the evolution of structure in aminoacyl-tRNA synthetases","volume":"67","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41573-019-0026-3","article-title":"Aminoacyl-tRNA synthetases as therapeutic targets","volume":"18","author":"Kwon","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1146\/annurev.biochem.69.1.617","article-title":"Aminoacyl-tRNA synthesis","volume":"69","author":"Ibba","year":"2000","journal-title":"Annu. Rev. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"16567","DOI":"10.1074\/jbc.M116.730812","article-title":"A WHEP Domain Regulates the Dynamic Structure and Activity of Caenorhabditis elegans Glycyl-tRNA Synthetase","volume":"291","author":"Chang","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"31559","DOI":"10.1074\/jbc.C000385200","article-title":"Active aminoacyl-tRNA synthetases are present in nuclei as a high molecular weight multienzyme complex","volume":"275","author":"Nathanson","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1093\/gbe\/evv095","article-title":"Dual Organellar Targeting of Aminoacyl-tRNA Synthetases in Diatoms and Cryptophytes","volume":"7","author":"Gile","year":"2015","journal-title":"Genome Biol. Evol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.1074\/jbc.REV118.002982","article-title":"Pathways to disease from natural variations in human cytoplasmic tRNAs","volume":"294","author":"Lant","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hasan, F., Lant, J.T., and O\u2019Donoghue, P. (2023). Perseverance of protein homeostasis despite mistranslation of glycine codons with alanine. Phil. Trans. R. Soc. B, 378.","DOI":"10.1098\/rstb.2022.0029"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R114","DOI":"10.1093\/hmg\/ddx231","article-title":"Emerging mechanisms of aminoacyl-tRNA synthetase mutations in recessive and dominant human disease","volume":"26","author":"Antonellis","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Turvey, A.K., Horvath, G.A., and Cavalcanti, A.R.O. (2022). Aminoacyl-tRNA synthetases in human health and disease. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.1029218"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S0006-291X(02)00525-9","article-title":"Genomic organization, transcriptional mapping, and evolutionary implications of the human bi-directional histidyl-tRNA synthetase locus (HARS\/HARSL)","volume":"294","author":"Miller","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/BF01539922","article-title":"Chromosomal localization of human gene for histidyl-tRNA synthetase: Clustering of genes encoding aminoacyl-tRNA synthetases on human chromosome 5","volume":"12","author":"Wasmuth","year":"1986","journal-title":"Somat. Cell Mol. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1093\/nar\/15.8.3349","article-title":"Isolation, structure and expression of mammalian genes for histidyl-tRNA synthetase","volume":"15","author":"Tsui","year":"1987","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3389\/fcell.2019.00067","article-title":"Knock-Down of Histidyl-tRNA Synthetase Causes Cell Cycle Arrest and Apoptosis of Neuronal Progenitor Cells in vivo","volume":"7","author":"Waldron","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1016\/j.str.2012.08.001","article-title":"Internally deleted human tRNA synthetase suggests evolutionary pressure for repurposing","volume":"20","author":"Xu","year":"2012","journal-title":"Structure"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/08916930400022640","article-title":"Anti-Jo-1 antibodies","volume":"38","author":"Zampieri","year":"2005","journal-title":"Autoimmunity"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chen, A.W., Jayasinghe, M.I., Chung, C.Z., Rao, B.S., Kenana, R., Heinemann, I.U., and Jackman, J.E. (2019). The Role of 3\u2032 to 5\u2032 Reverse RNA Polymerization in tRNA Fidelity and Repair. Genes, 10.","DOI":"10.3390\/genes10030250"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/nar\/gkr696","article-title":"tRNAHis-guanylyltransferase establishes tRNAHis identity","volume":"40","author":"Heinemann","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1261\/rna.032300.112","article-title":"Doing it in reverse: 3\u2032-to-5\u2032 polymerization by the Thg1 superfamily","volume":"18","author":"Jackman","year":"2012","journal-title":"RNA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1080\/15476286.2017.1372076","article-title":"Minimal requirements for reverse polymerization and tRNA repair by tRNAHis guanylyltransferase","volume":"15","author":"Desai","year":"2017","journal-title":"RNA Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21103","DOI":"10.1073\/pnas.0912072106","article-title":"The appearance of pyrrolysine in tRNAHis guanylyltransferase by neutral evolution","volume":"106","author":"Heinemann","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3567","DOI":"10.1016\/j.febslet.2010.07.023","article-title":"3\u2032-5\u2032 tRNAHis guanylyltransferase in bacteria","volume":"584","author":"Heinemann","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1021\/bi035708f","article-title":"G\u22121:C73 recognition by an arginine cluster in the active site of Escherichia coli histidyl-tRNA synthetase","volume":"43","author":"Connolly","year":"2004","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1261\/rna.048389.114","article-title":"Life without post-transcriptional addition of G-1: Two alternatives for tRNAHis identity in Eukarya","volume":"21","author":"Rao","year":"2014","journal-title":"RNA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5031","DOI":"10.1093\/nar\/22.23.5031","article-title":"Histidylation by yeast HisRS of tRNA or tRNA-like structure relies on residues\u20131 and 73 but is dependent on the RNA context","volume":"22","author":"Rudinger","year":"1994","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19440","DOI":"10.1073\/pnas.1908288116","article-title":"CMT disease severity correlates with mutation-induced open conformation of histidyl-tRNA synthetase, not aminoacylation loss, in patient cells","volume":"116","author":"Blocquel","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1093\/nar\/gkv129","article-title":"Structural basis for recognition of G-1-containing tRNA by histidyl-tRNA synthetase","volume":"43","author":"Tian","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7855","DOI":"10.1093\/nar\/17.19.7855","article-title":"Role of the extra G-C pair at the end of the acceptor stem of tRNAHb in aminoacylation","volume":"17","author":"Himeno","year":"1989","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1021\/bi0025316","article-title":"Covariation of a specificity-determining structural motif in an aminoacyl-tRNA synthetase and a tRNA identity element","volume":"40","author":"Hawko","year":"2001","journal-title":"Biochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.molcel.2007.01.015","article-title":"Kinetic discrimination of tRNA identity by the conserved motif 2 loop of a class II aminoacyl-tRNA synthetase","volume":"25","author":"Guth","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"20753","DOI":"10.1074\/jbc.M109.021311","article-title":"Asymmetric amino acid activation by class II histidyl-tRNA synthetase from Escherichia coli","volume":"284","author":"Guth","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.1021\/bi047923h","article-title":"A substrate-assisted concerted mechanism for aminoacylation by a class II aminoacyl-tRNA synthetase","volume":"44","author":"Guth","year":"2005","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1006\/bbrc.2002.6398","article-title":"Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex","volume":"291","author":"Lee","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/humu.22210","article-title":"A loss-of-function variant in the human histidyl-tRNA synthetase (HARS) gene is neurotoxic in vivo","volume":"34","author":"Vester","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1093\/brain\/awv158","article-title":"Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies","volume":"138","author":"Brozkova","year":"2015","journal-title":"Brain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1002\/acn3.791","article-title":"Peripheral neuropathy and cognitive impairment associated with a novel monoallelic HARS variant","volume":"6","author":"Tsouni","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/humu.23380","article-title":"Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy","volume":"39","author":"Abbott","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jmoldx.2015.10.005","article-title":"Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy","volume":"18","author":"Lupo","year":"2016","journal-title":"J. Mol. Diagn."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Puffenberger, E.G., Jinks, R.N., Sougnez, C., Cibulskis, K., Willert, R.A., Achilly, N.P., Cassidy, R.P., Fiorentini, C.J., Heiken, K.F., and Lawrence, J.J. (2012). Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0028936"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nchembio.1339","article-title":"Upgrading protein synthesis for synthetic biology","volume":"9","author":"Ling","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1016\/j.febslet.2012.08.031","article-title":"Enhanced phosphoserine insertion during Escherichia coli protein synthesis via partial UAG codon reassignment and release factor 1 deletion","volume":"586","author":"Heinemann","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"16724","DOI":"10.1073\/pnas.1419737111","article-title":"Polyspecific pyrrolysyl-tRNA synthetases from directed evolution","volume":"111","author":"Guo","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1080\/15476286.2017.1379645","article-title":"Visualizing tRNA-dependent mistranslation in human cells","volume":"15","author":"Lant","year":"2017","journal-title":"RNA Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11883","DOI":"10.1093\/nar\/gkab898","article-title":"Formation and persistence of polyglutamine aggregates in mistranslating cells","volume":"49","author":"Lant","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/15476286.2021.2015173","article-title":"A novel fluorescent reporter sensitive to serine mis-incorporation","volume":"19","author":"Rozik","year":"2022","journal-title":"RNA Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.neuron.2017.09.057","article-title":"Regulation of mRNA Translation in Neurons\u2014A Matter of Life and Death","volume":"96","author":"Kapur","year":"2017","journal-title":"Neuron"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Qiu, Y., Kenana, R., Beharry, A., Wilhelm, S.D.P., Hsu, S.Y., Siu, V.M., Duennwald, M., and Heinemann, I.U. (2022). Histidine supplementation can escalate or rescue HARS deficiency in a Charcot\u2013Marie\u2013Tooth Disease model. Hum. Mol. Genet., ddac239.","DOI":"10.1093\/hmg\/ddac239"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/febs.15449","article-title":"Neuropathy-associated histidyl-tRNA synthetase variants attenuate protein synthesis in vitro and disrupt axon outgrowth in developing zebrafish","volume":"288","author":"Mullen","year":"2020","journal-title":"FEBS J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1021\/acs.biochem.7b00114","article-title":"The Usher Syndrome Type IIIB Histidyl-tRNA Synthetase Mutation Confers Temperature Sensitivity","volume":"56","author":"Abbott","year":"2017","journal-title":"Biochemistry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e029240","DOI":"10.1136\/bmjopen-2019-029240","article-title":"Prevalence of Charcot-Marie-Tooth disease across the lifespan: A population-based epidemiological study","volume":"9","author":"Theadom","year":"2019","journal-title":"BMJ Open"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000443706","article-title":"Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review","volume":"46","author":"Barreto","year":"2016","journal-title":"Neuroepidemiology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/S1474-4422(09)70110-3","article-title":"Diagnosis, natural history, and management of Charcot-Marie-Tooth disease","volume":"8","author":"Pareyson","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/ejhg.2009.31","article-title":"Charcot-Marie-Tooth disease","volume":"17","author":"Szigeti","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/ana.10089","article-title":"Charcot-Marie-Tooth disease and related neuropathies: Mutation distribution and genotype-phenotype correlation","volume":"51","author":"Boerkoel","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5321","DOI":"10.1074\/jbc.REV118.002955","article-title":"Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases","volume":"294","author":"Wei","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1086\/375039","article-title":"Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V","volume":"72","author":"Antonellis","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/ng1727","article-title":"Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy","volume":"38","author":"Jordanova","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ajhg.2009.12.005","article-title":"A major determinant for binding and aminoacylation of tRNAAla in cytoplasmic alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease","volume":"86","author":"Latour","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1136\/jnnp-2013-305049","article-title":"Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2","volume":"84","author":"Gonzalez","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e2205669119","DOI":"10.1073\/pnas.2205669119","article-title":"Multimodal cotranslational interactions direct assembly of the human multi-tRNA synthetase complex","volume":"119","author":"Khan","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","first-page":"417217","article-title":"An Update on the Genetics of Usher Syndrome","volume":"2011","author":"Aller","year":"2010","journal-title":"J. Ophthalmol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13023-014-0168-7","article-title":"Targeted next generation sequencing for molecular diagnosis of Usher syndrome","volume":"9","author":"Aparisi","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"565216","DOI":"10.3389\/fgene.2020.565216","article-title":"Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy","volume":"11","author":"Whatley","year":"2020","journal-title":"Front. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.devcel.2015.12.020","article-title":"Mechanistic Basis of Organization of the Harmonin\/USH1C-Mediated Brush Border Microvilli Tip-Link Complex","volume":"36","author":"Li","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3389\/fnmol.2017.00401","article-title":"Loss of CIB2 Causes Profound Hearing Loss and Abolishes Mechanoelectrical Transduction in Mice","volume":"10","author":"Wang","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_70","first-page":"367","article-title":"The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort","volume":"19","author":"Besnard","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1126\/science.280.5370.1753","article-title":"Mutation of a gene encoding a protein with extracellular matrix motifs in usher syndrome type IIa","volume":"280","author":"Eudy","year":"1998","journal-title":"Science"},{"key":"ref_72","first-page":"624","article-title":"The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells","volume":"26","author":"Zou","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/hmg\/4.1.93","article-title":"Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q","volume":"4","author":"Sankila","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1086\/323610","article-title":"Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3","volume":"69","author":"Joensuu","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_75","first-page":"1806","article-title":"Disease-causing mutations in the CLRN1 gene alter normal CLRN1 protein trafficking to the plasma membrane","volume":"15","author":"Isosomppi","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1172\/JCI94351","article-title":"Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome","volume":"128","author":"Dulon","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/s41598-017-01577-8","article-title":"A deep intronic CLRN1 (USH3A) founder mutation generates an aberrant exon and underlies severe Usher syndrome on the Arabian Peninsula","volume":"7","author":"Khan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.biochi.2014.08.005","article-title":"Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases","volume":"106","author":"Koh","year":"2014","journal-title":"Biochimie"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/1873-3468.12962","article-title":"The role of tRNA synthetases in neurological and neuromuscular disorders","volume":"592","author":"Boczonadi","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00393-019-0665-0","article-title":"Antisynthetase syndrome","volume":"78","author":"Bauhammer","year":"2019","journal-title":"Z. Rheumatol."},{"key":"ref_81","first-page":"e00300","article-title":"Exogenous d-\u03b2-hydroxybutyrate lowers blood glucose in part by decreasing the availability of L-alanine for gluconeogenesis","volume":"5","author":"Norwitz","year":"2021","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2588S","DOI":"10.1093\/jn\/nxaa229","article-title":"Benefits and Adverse Effects of Histidine Supplementation","volume":"150","author":"Gheller","year":"2020","journal-title":"J. Nutr."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1293\/tox.2013-0026","article-title":"A 4-week Repeated Dose Toxicity Study of Glycine in Rats by Gavage Administration","volume":"26","author":"Shibui","year":"2013","journal-title":"J. Toxicol. Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1126\/science.abb3356","article-title":"tRNA overexpression rescues peripheral neuropathy caused by mutations in tRNA synthetase","volume":"373","author":"Zuko","year":"2021","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3850","DOI":"10.1038\/s41467-021-24076-x","article-title":"Repurposing tRNAs for nonsense suppression","volume":"12","author":"Albers","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41586-022-04533-3","article-title":"AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice","volume":"604","author":"Wang","year":"2022","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41576-021-00439-4","article-title":"Drug delivery systems for RNA therapeutics","volume":"23","author":"Paunovska","year":"2022","journal-title":"Nat. Rev. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/254\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:09:25Z","timestamp":1760119765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":87,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["genes14020254"],"URL":"https:\/\/doi.org\/10.3390\/genes14020254","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]}}}