Ask about this productRelated genes to: YARS Blocking Peptide
- Gene:
- YARS NIH gene
- Name:
- tyrosyl-tRNA synthetase
- Previous symbol:
- -
- Synonyms:
- YTS, YRS, tyrRS
- Chromosome:
- 1p35.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-29
- Date modifiied:
- 2019-04-23
Related products to: YARS Blocking Peptide
Related articles to: YARS Blocking Peptide
- Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy characterized by sensory dysfunction and muscle weakness, manifesting in the most distal limbs first and progressing more proximal. Over a hundred genes are currently linked to CMT with enrichment for activities in myelination, axon transport, and protein synthesis. Mutations in tRNA synthetases cause dominantly inherited forms of CMT, and animal models with CMT-linked mutations in these enzymes display defects in neuronal protein synthesis. Rescuing protein synthesis in CMT-mutant neurons could offer exciting therapeutic options beyond symptom management. To address this need, we expressed CMT-linked variants of tyrosyl-tRNA synthetase (YARS-CMT) in primary mouse sensory neurons derived from both male and female embryos and evaluated impacts on protein synthesis and cell viability. YARS-CMT expression reduced protein synthesis in these neurons prior to the onset of caspase-dependent axon degeneration and cell death. To determine how YARS-CMT expression affects axon outgrowth, we dissociated and replated these neurons to stimulate axon regeneration. To our surprise, axonal regrowth occurred normally in replated YARS-CMT neurons. Moreover, replating YARS-CMT neurons rescued protein synthesis. Inhibiting mammalian target of rapamycin suppressed rescue of protein synthesis after replating, consistent with its significant role in protein synthesis during axon regeneration. These discoveries identify new avenues for augmenting protein synthesis in diseased neurons and restoring protein synthesis in CMT or other neurological disorders. - Source: PubMed
Publication date: 2026/03/27
Koenig JuliannaMcGuire AlexysHomedan YaraAlberhasky JessicaSummers Daniel W - Reference sequences are essential for reproducible genetic analyses but are often chosen without regard to evolutionary relevance within the analyzed species. The human Y chromosome is widely used in evolutionary studies, yet current references represent evolutionarily young sequences, which can cause misleading variant calling. To address this issue, we constructed a Y-chromosomal ancestral-like reference sequence to improve the detection of evolutionarily informative variants on the Y chromosome. The Y-chromosomal ancestral-like reference sequence was constructed by applying a weighted maximum parsimony approach to human and primate Y chromosome sequences. To benchmark the performance of the Y-chromosomal ancestral-like reference sequence, 40 Y chromosome short-read sequences from diverse haplogroups were aligned to Y-chromosomal ancestral-like reference sequence and existing references (GRCh37, GRCh38, and T2T-CHM13). Overall, the Y-chromosomal ancestral-like reference sequence yielded the highest and most consistent number of SNPs per sample (mean = 1,400; SD = 77), while other references yielded on average fewer variants (mean = 866 to 968) and showed greater variability across samples (SD = 457 to 531) depending on their phylogenetic distance from the reference. Additionally, alignments to the Y-chromosomal ancestral-like reference sequence resulted in calling solely SNPs with evolutionarily derived alleles, while alignments to other references resulted in calling on average 46% SNPs with ancestral alleles. This study demonstrates how the existing reference sequences fail to capture the full range of evolutionary information on the Y chromosome. The Y-chromosomal ancestral-like reference sequence improves capturing evolutionary information on the Y chromosome, making it a valuable resource for various evolutionary applications, such as TMRCA estimations and phylogenetic analyses. Finally, alongside the Y-chromosomal ancestral-like reference sequence, we provide a publicly available tool, polaryzer, to annotate variants as ancestral or derived in pre-aligned Y chromosome data. - Source: PubMed
Köksal ZehraPreussner AnninaLeinonen JaakkoTukiainen Taru - Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy characterized by sensory dysfunction and muscle weakness, manifesting in the most distal limbs first and progressing more proximal. Over a hundred genes are currently linked to CMT with enrichment for activities in myelination, axon transport, and protein synthesis. Mutations in tRNA synthetases cause dominantly inherited forms of CMT and animal models with CMT-linked mutations in these enzymes display defects in neuronal protein synthesis. Rescuing protein synthesis in CMT mutant neurons could offer exciting therapeutic options beyond symptom management. To address this need, we expressed CMT-linked variants in tyrosyl tRNA synthetase (YARS-CMT) in primary sensory neurons and evaluated impacts on protein synthesis and cell viability. YARS-CMT expression reduced protein synthesis in these neurons prior to the onset of caspase-dependent axon degeneration and cell death. To determine how YARS-CMT expression affects axon outgrowth, we dissociated and replated these neurons to stimulate axon regeneration. To our surprise, axonal regrowth occurred normally in replated YARS-CMT neurons. Moreover, replating YARS-CMT neurons rescued protein synthesis. Inhibiting mTOR suppressed rescue of protein synthesis after replating, consistent with its significant role in protein synthesis during axon regeneration. These discoveries identify new avenues for augmenting protein synthesis in diseased neurons and restoring protein synthesis in CMT or other neurological disorders. - Source: PubMed
Publication date: 2025/08/31
Koenig JuliannaMcGuire AlexysHomedan YaraAlberhasky JessicaSummers Daniel W - This study, the first of its kind in Colombia, aimed to investigate the relationship between respiratory symptoms and exposure to biological risks among informal waste pickers. - Source: PubMed
Rozo Silva Yenny AndreaCalderón Sierra Leidy IsabelAguilar-Elena Raúl - Senescence is a tumor suppressor mechanism triggered by oncogene expression and chemotherapy treatment. It orchestrates a definitive cessation of cell proliferation through the activation of the p53-p21 and p16-Rb pathways, coupled with the compaction of proliferative genes within heterochromatin regions. Some cancer cells have the ability to elude this proliferative arrest but the signaling pathways involved in circumventing senescence remain to be characterized. We have recently described that malignant cells capable of evading senescence have an increased expression of specific tRNAs, such as tRNA-Leu-CAA and tRNA-Tyr-GTA, alongside the activation of their corresponding tRNA ligases, namely LARS and YARS. We have previously shown that YARS promotes senescence escape by activating proliferation and cell cycle genes but its functions during this proliferative arrest remain largely unknown. In this study, we have continued to characterize the functions of YARS, describing non-canonical transcriptional functions of the ligase. Our results show that YARS is present in the nucleus of proliferating and senescent cells and interacts with the Trim28 transcriptional regulator. Importantly, YARS binds to the LIN9 promoter, a critical member of the Dream complex responsible for regulating cell cycle gene transcription. The ligase facilitates the binding and the phosphorylation of the type II RNA polymerase and promotes the deposition of activating epigenetic marks on the LIN9 promoter. Consequently, during senescence escape, YARS activates LIN9 expression and both proteins are necessary to induce the proliferation of emergent cells. These results underscore unconventional transcriptional functions of YARS in activating LIN9 expression in proliferating cells and during senescence escape. - Source: PubMed
Publication date: 2025/01/05
Coquelet HugoLeman GeraldineMaarouf AminePetit CoralieToutain BertrandHenry CécileBoissard AliceGuette CatherineLelièvre EricVidi Pierre-AlexandreGuillon JordanCoqueret Olivier