A5002688120- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Hereditary Neurological Disorders
- Genomics and Phylogenetic Studies
- RNA regulation and disease
- Cancer-related molecular mechanisms research
- DNA and Nucleic Acid Chemistry
- Cell Adhesion Molecules Research
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- Signaling Pathways in Disease
- Cancer therapeutics and mechanisms
- Advanced biosensing and bioanalysis techniques
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Protein Structure and Dynamics
- S100 Proteins and Annexins
- Chemical Synthesis and Analysis
- interferon and immune responses
- Bioactive Compounds and Antitumor Agents
- Machine Learning in Bioinformatics
- Cellular transport and secretion
- Nerve injury and regeneration
- Antimicrobial Peptides and Activities
Scripps Research Institute
2016-2025
Scripps Laboratories (United States)
2014-2022
Hong Kong University of Science and Technology
2012-2018
University of Hong Kong
2012-2018
University of Antwerp
2017
University of Belgrade
2017
University Children's Hospital, Belgrade
2017
University Hospital of Zurich
2017
University of Zurich
2017
Shanghai Ninth People's Hospital
2013
In higher eukaryotes, transfer RNAs (tRNAs) with the same anticodon are encoded by multiple nuclear genes, and little is known about how mutations in these genes affect translation cellular homeostasis. Similarly, surveillance systems that respond to such defects eukaryotes not clear. Here, we discover loss of GTPBP2, a novel binding partner ribosome recycling protein Pelota, mice mutation tRNA gene specifically expressed central nervous system causes stalling widespread neurodegeneration....
Although adaptive systems of immunity against tumor initiation and destruction are well investigated, less understood is the role, if any, endogenous factors that have conventional functions. Here we show glycyl-tRNA synthetase (GRS), an essential component translation apparatus, circulates in serum can be secreted from macrophages response to Fas ligand released cells. Through cadherin (CDH)6 (K-cadherin), GRS bound different ERK-activated cells, phosphatase 2A (PP2A) CDH6. The activated...
Abstract Dominant mutations in five tRNA synthetases cause Charcot–Marie–Tooth (CMT) neuropathy, suggesting that altered aminoacylation function underlies the disease. However, previous studies showed loss of activity is not required to CMT. Here we present a Drosophila model for CMT with glycyl-tRNA synthetase (GARS). Expression three CMT-mutant GARS proteins induces defects motor performance and sensory neuron morphology, shortens lifespan. Mutant display normal subcellular localization...
Charcot–Marie–Tooth (CMT) disease is a genetically heterogeneous condition with >50 genes now being identified. Thanks to new technological developments, namely, exome sequencing, the ability identify additional rare in CMT has been drastically improved. Here we present data suggesting that <i>MARS</i> very novel cause of late-onset CMT2. This supported by strong functional and evolutionary evidence, yet absence unrelated cases warrant future studies substantiate this conclusion.
Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). In addition to GARS, three other tRNA genes cause similar neuropathies, although underlying mechanisms are not fully understood. To address this, we generated transgenic mice that ubiquitously over-express wild-type GARS and crossed them two dominant mouse models of CMT2D distinguish loss-of-function gain-of-function mechanisms....
Evolving from an enzyme and into a regulator Proteins, the work-horses of cell, are made on messenger RNA (mRNA) template. An called aminoacyl tRNA synthetases (AARSs) attaches correct amino acid to transfer so that mRNA is accurately translated. Over evolution, additional sequences have been added AARSs. Lo et al. found large number AARS variants in which domain responsible for function was deleted. Ninety-four such had diverse signaling activities. Thus, AARSs used both as enzymes...
Dominant mutations in glycyl-tRNA synthetase (GlyRS) cause a subtype of Charcot-Marie-Tooth neuropathy (CMT2D). Although previous studies have shown that GlyRS mutants aberrantly interact with Nrp1, giving insight into the disease's specific effects on motor neurons, these cannot explain length-dependent axonal degeneration. Here, we report HDAC6 and stimulate its deacetylase activity α-tubulin. A decrease α-tubulin acetylation deficits transport are observed mice peripheral nerves prior to...
Recent studies suggested an essential role for seryl-tRNA synthetase (SerRS) in vascular development. This is specific to SerRS among all tRNA synthetases and independent of its well-known aminoacylation function protein synthesis. A unique nucleus-directing domain, added at the invertebrate-to-vertebrate transition, confers this novel non-translational activity SerRS. Previous showed that SerRS, some unknown way, controls VEGFA expression prevent over-expansion. Using vitro, cell animal...
Charcot-Marie-Tooth (CMT) diseases are the most common heritable peripheral neuropathy. At least 10 different mutant alleles of GARS (the gene for glycyl-tRNA synthetase) have been reported to cause a dominant axonal form CMT (type 2D). A unifying connection between these mutations and has unclear. Here, mapping onto recently determined crystal structure human GlyRS showed them within band encompassing both sides dimer interface, with two CMT-causing being at sites that complementary...
New domains were progressively added to cytoplasmic aminoacyl transfer RNA (tRNA) synthetases during evolution. One example is the UNE-S domain, appended seryl-tRNA synthetase (SerRS) in species that developed closed circulatory systems. Here we show using solution and crystal structure analyses vitro vivo functional studies harbours a robust nuclear localization signal (NLS) directing SerRS nucleus where it attenuates vascular endothelial growth factor A expression. We also mutants...
Dominant-intermediate Charcot–Marie–Tooth neuropathy (DI-CMT) is characterized by axonal degeneration and demyelination of peripheral motor sensory neurons. Three dominant mutations in the YARS gene, encoding tyrosyl-tRNA synthetase (TyrRS), have so far been associated with DI-CMT type C. The molecular mechanisms through which lead to are currently unknown, animal models for DI-CMTC not yet available. Here, we report generation a Drosophila model DI-CMTC: expression 3 mutant—but wild...
Charcot-Marie-Tooth disease type 2D (CMT2D) is a peripheral nerve disorder caused by dominant, toxic, gain-of-function mutations in the widely expressed, housekeeping gene, GARS The mechanisms underlying selective pathology CMT2D remain unresolved, as does cause of mild-to-moderate sensory involvement that distinguishes from allelic distal spinal muscular atrophy V. To elucidate mechanism responsible for afferent pathology, we examined nervous system mice. We show equilibrium between...
<h3>Objective:</h3> To identify the unknown genetic cause in a nuclear family with an axonal form of peripheral neuropathy and atypical disease course. <h3>Methods:</h3> Detailed neurologic, electrophysiologic, neuropathologic examinations patients were performed. Whole exome sequencing both affected individuals was done. The effect identified sequence variations investigated at cDNA protein level patient-derived lymphoblasts. plasma sphingoid base profile analyzed. Functional consequences...