TARS Human
Description
Introduction to TARS Human (Threonyl-tRNA Synthetase 1)
TARS Human, encoded by the TARS1 gene, is a cytoplasmic threonyl-tRNA synthetase responsible for catalyzing the attachment of threonine to its cognate tRNA during protein synthesis. This enzyme belongs to the class-II aminoacyl-tRNA synthetase family, which plays a critical role in maintaining the fidelity of translation by ensuring accurate amino acid-tRNA pairing . The TARS1 gene is located on human chromosome 5 and is highly conserved across eukaryotes, underscoring its evolutionary importance .
Molecular Structure and Functional Mechanism
TARS Human exhibits a modular architecture typical of class-II synthetases, featuring:
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N-terminal extension: Specific to cytoplasmic threonyl-tRNA synthetases.
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N1 and N2 domains: Regulate editing activity to correct misacylation errors.
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Aminoacylation domain: Catalyzes the ATP-dependent formation of threonine-AMP.
Disease Associations
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Trichothiodystrophy 7, Nonphotosensitive: Linked to recessive TARS1 mutations, causing impaired translation fidelity and clinical features like brittle hair, skin abnormalities, and developmental delays .
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Cancer Risk: While TARS1 itself is not directly carcinogenic, its dysfunction may contribute to cellular stress in genetic disorders .
Pathogenic Mutations
Experimental modeling in Saccharomyces cerevisiae revealed loss-of-function mutations in conserved residues:
These mutations disrupt critical domains, highlighting the enzyme’s sensitivity to structural perturbations .
Humanized Yeast Models
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Complementation Assays: Yeast strains lacking endogenous THS1 (yeast ortholog of TARS1) are used to test human TARS1 variants. Wild-type TARS1 restores viability, while pathogenic mutations (e.g., R433H) fail to complement, confirming their functional impact .
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Dual ThrRS Systems: Mammals possess two cytoplasmic threonyl-tRNA synthetases: TARS1 and TARS-like (TARSL2). TARS1 is cytoplasmic, while TARSL2 localizes to the nucleus, suggesting distinct roles in translation regulation .
Recombinant Production
TARS Human is produced in Escherichia coli as a recombinant protein with a His-tag for purification. This form is used in biochemical studies to analyze catalytic mechanisms, tRNA binding, and editing efficiency .
Therapeutic and Diagnostic Potential
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Trichothiodystrophy Research: TARS1 mutations serve as biomarkers for diagnosing nonphotosensitive trichothiodystrophy, guiding personalized therapeutic strategies .
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Anticancer Targets: Dysregulation of tRNA synthetases in cancer cells may offer avenues for targeted therapies, though TARS1-specific applications remain under investigation .
Product Specs
GSCFFLPKGA YIYNALIEFI RSEYRKRGFQ EVVTPNIFNS RLWMTSGHWQ HYSENMFSFE VEKELFALKP MNCPGHCLMF DHRPRSWREL PLRLADFGVL HRNELSGALT GLTRVRRFQQ DDAHIFCAME QIEDEIKGCL DFLRTVYSVF GFSFKLNLST RPEKFLGDIE VWDQAEKQLE NSLNEFGEKW ELNSGDGAFY GPKIDIQIKD AIGRYHQCAT IQLDFQLPIR FNLTYVSHDG DDKKRPVIVH RAILGSVERM IAILTENYGG KWPFWLSPRQ VMVVPVGPTC DEYAQKVRQQ FHDAKFMADI DLDPGCTLNK KIRNAQLAQY NFILVVGEKE KISGTVNIRT RDNKVHGERT ISETIERLQQ LKEFRSKQAE EEF.
Q&A
What is human TARS and what methodologies should be used to study its function?
Human TARS (Threonyl-tRNA Synthetase) is an essential enzyme involved in protein synthesis, specifically responsible for attaching threonine to its cognate tRNA molecule. This 743 amino acid protein (85.6kDa) plays a crucial role in translation accuracy .
Methodological approach:
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For protein-level studies: Utilize recombinant TARS human protein expressed in E. coli systems with N-terminal His-tag for purification via chromatographic techniques
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For quantitative analysis: Employ ELISA-based detection in various human samples (serum, plasma, cell lysates)
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For gene-level studies: Consider TAR (Transformation-Associated Recombination) cloning for accurate isolation of the full-length gene with all regulatory elements
How can researchers distinguish between different forms of TARS in experimental workflows?
TARS exists in different forms including cytoplasmic TARS (the primary form) versus potential mitochondrial variants .
Methodological approach:
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Employ compartment-specific isolation techniques (subcellular fractionation)
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Use form-specific ELISA kits designed for cytoplasmic TARS detection
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Design experiments that account for potential isoform differences when measuring TARS activity
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Consider differential expression analysis across cellular compartments
What are the fundamental experimental considerations when working with recombinant TARS?
Methodological approach:
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Expression system selection: E. coli systems have been validated for producing functional, non-glycosylated TARS
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Purification strategy: Utilize His-tag fusion proteins (20 amino acid His-tag at N-terminus) for affinity purification
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Quality control: Verify molecular weight (expected 85.6kDa) and amino acid sequence integrity
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Storage conditions: Follow manufacturer recommendations for maintaining enzyme activity
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Activity assays: Design appropriate aminoacylation assays to measure functional activity
What methodological approaches should researchers use to investigate TARS in disease contexts?
TARS dysregulation has been linked to various diseases including cancer, neurological disorders, and metabolic diseases .
Methodological approach:
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Biomarker studies: Use specialized ELISA kits to quantify TARS levels in patient samples versus controls
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Genetic analysis: Apply TAR cloning to isolate and study variant TARS alleles from patient populations
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Functional impact assessment: Develop assays that measure both canonical (aminoacylation) and non-canonical functions
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Disease model development: Consider both cell and animal models expressing disease-associated TARS variants
| Disease Category | Recommended Methodological Approach | Sample Types | Analysis Method |
|---|---|---|---|
| Cancer | Comparative expression profiling | Tumor/normal tissue pairs | ELISA, immunohistochemistry |
| Neurological disorders | Functional activity assessment | CSF, neuronal cultures | Aminoacylation assays |
| Metabolic diseases | Protein-interaction studies | Metabolic tissues | Co-immunoprecipitation |
How can researchers effectively study structural variations in the TARS gene across human populations?
Methodological approach:
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Apply TAR cloning technology which allows selective, accurate, and efficient isolation of genomic fragments from complex genomes
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Combine with CRISPR/Cas9 pre-treatment of genomic DNA to increase yield of gene-positive clones by up to 32%
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Use TAR cloning to discover and characterize structural variations causing Mendelian disorders
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Sequence TAR-isolated human genes to identify variant alleles and regulatory elements
What experimental design best captures the evolutionary significance of TARS?
Methodological approach:
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Comparative genomics: Analyze conserved segments between human TARS and homologs in other species
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Structural biology: Examine conserved domains versus species-specific regions
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Functional conservation: Design aminoacylation assays testing cross-species compatibility
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Evolutionary pressure analysis: Compare synonymous vs. non-synonymous mutations
TAR cloning studies have revealed that some variants in human genetic material show conservation between human and yeast, suggesting fundamental evolutionary importance . This approach could be applied to TARS research to understand evolutionary constraints on this essential enzyme.
How should researchers apply the TARS model for text analysis in scientific applications?
The TARS model architecture extends pre-trained BERT models with support for fine-tuning on text classification tasks using few-shot learning techniques .
Methodological approach:
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Model selection: Use TARS when dealing with non-homogeneous data requiring domain expertise for labeling
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Training strategy: Implement explicit negative examples to improve model discrimination capability
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Performance optimization: Consider cross-training to improve precision and recall (demonstrated improvement from F1 score of 0.67 to 0.76 in studies)
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Evaluation metrics: Track precision, recall, and F1 scores to assess model performance
| Method | Precision | Recall | F1 score | Training Examples |
|---|---|---|---|---|
| OpenTag | 0.84 | 0.65 | 0.72 | ~27,000 (weak supervision) |
| TARS without cross-training | 0.75 | 0.64 | 0.67 | 40 (gold dataset) |
| TARS with cross-training | 0.84 | 0.72 | 0.76 | 40 (gold dataset) |
Table data extracted from research comparing TARS model performance with other methods
How can researchers effectively design studies on human-AI interaction using TARS methodology?
The Terascale All-sensing Research Studio (TARS) at Wright State University conducts research on human-driven artificial intelligence through analysis of multi-person interactions .
Methodological approach:
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Research design: Focus on dense multi-person interactions in both online and real-world environments
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Interdisciplinary integration: Combine computer vision, graphics, deep learning, and human-robot interaction methodologies
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Application domains: Consider virtual reality environments for data collection on human behavior
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Data annotation: Utilize VR-based hand tracking for hand-object interaction studies
Recent publications from TARS researchers demonstrate methodological innovations such as:
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Analyzing giver and receiver timing relationships during pre-handover phases
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Using motion forecasting for behavior-based VR authentication
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Developing VR-based hand tracking for hand-object data annotation
What methodological considerations should guide research on TARS-style personality parameters in AI systems?
Inspired by the fictional TARS from Interstellar, researchers might explore personality trait parameters in AI systems .
Methodological approach:
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Parameter design: Consider adjustable traits like honesty, humor, discretion, and trust levels
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Analysis of social engagement: Study how personality parameters influence human-AI conversation patterns
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Ethical considerations: Evaluate how trust settings affect AI decision-making in critical scenarios
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Balancing autonomy and control: Assess how personality parameters enable human-like intelligence while maintaining appropriate restrictions
How might researchers bridge biological TARS studies with AI systems for improved biomedical applications?
Methodological approach:
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AI-assisted genomics: Apply TARS few-shot learning to analyze TARS gene variants in large datasets
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Structural prediction: Use AI systems to model TARS protein interactions and predict functional impacts of mutations
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Diagnostic tool development: Create systems that integrate biological TARS markers with AI-based pattern recognition
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Therapeutic discovery: Implement machine learning approaches to identify compounds affecting TARS function
What experimental design considerations are important when studying TARS across different research domains?
Methodological approach:
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Terminology disambiguation: Clearly define TARS context (biological enzyme vs. AI system)
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Cross-domain collaboration: Establish interdisciplinary teams with expertise in both biochemistry and computer science
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Standardized reporting: Develop consistent frameworks for describing TARS methodologies across domains
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Technology transfer: Identify methodological approaches that can be adapted between biological and computational TARS research
How should researchers approach sample preparation for TARS-related experiments?
For biological TARS studies:
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Recombinant production: E. coli expression systems have been validated for producing single, non-glycosylated polypeptide chain TARS human protein
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Purification approach: Utilize His-tag fusion and proprietary chromatographic techniques
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Sample types: Process serum, plasma, or cell lysates for ELISA-based detection
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Genomic material: For gene studies, implement TAR cloning methodologies for high-fidelity isolation
For TARS AI model training:
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Data preparation: Select representative examples for few-shot learning scenarios
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Negative example selection: Implement explicit negative examples to improve model discrimination
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Cross-domain training: Consider training across related domains to improve model generalization
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Synthetic data generation: Complement human-labeled data with synthetically produced training data
Product Science Overview
Threonyl-tRNA synthetase (ThrRS) is an essential enzyme in the process of protein synthesis. It belongs to the family of aminoacyl-tRNA synthetases (aaRSs), which are responsible for the aminoacylation of transfer RNA (tRNA) molecules with their corresponding amino acids. This process is crucial for the accurate translation of genetic information from mRNA into proteins.
Threonyl-tRNA synthetase is a cytoplasmic enzyme encoded by the TARS gene in humans . The primary function of ThrRS is to catalyze the attachment of the amino acid threonine to its corresponding tRNA (tRNA^Thr). This reaction involves the formation of a threonyl-adenylate intermediate, followed by the transfer of threonine to the 3’ end of the tRNA molecule.
The enzyme’s structure is highly conserved across different species, reflecting its fundamental role in cellular biology. ThrRS typically consists of a catalytic domain responsible for the aminoacylation reaction and an anticodon-binding domain that ensures the correct tRNA is recognized and charged with threonine.
Threonyl-tRNA synthetase plays a critical role in maintaining the fidelity of protein synthesis. By ensuring that tRNA molecules are accurately charged with their corresponding amino acids, ThrRS helps prevent errors in the translation process that could lead to the production of dysfunctional proteins.
In addition to its canonical role in translation, ThrRS has been implicated in various cellular processes beyond protein synthesis. For instance, it has been detected extracellularly in autoimmune diseases and has exhibited pro-angiogenetic activity . This suggests that ThrRS may have additional functions in immune regulation and vascular biology.
Human recombinant Threonyl-tRNA synthetase is produced using recombinant DNA technology. This involves cloning the TARS gene into an expression vector, which is then introduced into a suitable host organism, such as Escherichia coli. The host cells are cultured under conditions that promote the expression of the recombinant protein, which is subsequently purified using chromatographic techniques.
Recombinant ThrRS is used in various research applications, including studies on protein synthesis, enzyme kinetics, and the development of therapeutic agents targeting aaRSs. Its availability as a recombinant protein allows for detailed biochemical and structural analyses, which are essential for understanding its function and potential roles in disease.
The study of Threonyl-tRNA synthetase has significant implications for both basic research and clinical applications. In the context of infectious diseases, for example, the enzyme has been explored as a potential therapeutic target for the treatment of parasitic infections such as visceral leishmaniasis . In this case, inhibitors of ThrRS could disrupt protein synthesis in the parasite, leading to its elimination.
Moreover, the involvement of ThrRS in immune responses and angiogenesis highlights its potential as a target for therapeutic intervention in autoimmune diseases and cancer. By modulating the activity of ThrRS, it may be possible to influence these pathological processes and develop novel treatments.
