A5047797998- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Bacteriophages and microbial interactions
- Vibrio bacteria research studies
- Enzyme Structure and Function
- RNA regulation and disease
- Protein Structure and Dynamics
- Gene Regulatory Network Analysis
- Microbial Metabolic Engineering and Bioproduction
- Endoplasmic Reticulum Stress and Disease
- Immune Response and Inflammation
- Salmonella and Campylobacter epidemiology
- Chemical Synthesis and Analysis
- Cell Image Analysis Techniques
- Machine Learning in Bioinformatics
- Immune cells in cancer
- Mitochondrial Function and Pathology
- interferon and immune responses
- Bacterial Identification and Susceptibility Testing
- Viral gastroenteritis research and epidemiology
- Aquaculture disease management and microbiota
University of Maryland, College Park
2018-2025
The University of Texas Health Science Center at Houston
2013-2019
The University of Texas MD Anderson Cancer Center
2018
Houston Graduate School of Theology
2017
University of Macau
2016
Guangdong University of Technology
2016
Yale University
2010-2014
University of Houston
2014
Whitney Museum of American Art
2013
State Library of Ohio
2010
Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception inborn errors of metabolism, since many these disorders are responsive to therapy that targets pathophysiological features at molecular or cellular level.To uncover genetic basis potentially treatable we combined deep clinical phenotyping (the comprehensive...
Oxidative stress arises from excessive reactive oxygen species (ROS) and affects organisms of all three domains life. Here we present a previously unknown pathway through which ROS may impact faithful protein synthesis. Aminoacyl-tRNA synthetases are key enzymes in the translation genetic code; they attach correct amino acid to each tRNA hydrolyze an incorrectly attached process called editing. We show both vitro vivo Escherichia coli that reduced overall translational fidelity by impairing...
Abstract Accurate flow of genetic information from DNA to protein requires faithful translation. An increased level translational errors (mistranslation) has therefore been widely considered harmful cells. Here we demonstrate that surprisingly, moderate levels mistranslation indeed increase tolerance oxidative stress in Escherichia coli. Our RNA sequencing analyses revealed two antioxidant genes katE and osmC, both controlled by the general response activator RpoS, were upregulated a...
Over 300 amino acids are found in proteins nature, yet typically only 20 genetically encoded. Reassigning stop codons and use of quadruplet emerged as the main avenues for encoding non‐canonical (NCAAs). Canonical aminoacyl‐tRNAs with near‐cognate anticodons also read these to some extent. This background suppression leads ‘statistical protein’ that contains natural acid(s) at a site intended NCAA. We characterize amber, opal codon common Escherichia coli laboratory strains find PylRS/tRNA...
The protein translational system, including transfer RNAs (tRNAs) and several categories of enzymes, plays a key role in regulating cell proliferation. Translation dysregulation also contributes to cancer development, though relatively little is known about the changes that occur system cancer. Here, we present global analyses tRNAs three enzymes involved regulation ~10,000 patients across 31 types from Cancer Genome Atlas. By analyzing expression levels at gene, codon, amino acid levels,...
Accurate selection of amino acids is essential for faithful translation the genetic code. Errors during acid are usually corrected by editing activity aminoacyl-tRNA synthetases such as phenylalanyl-tRNA (PheRS), which edit misactivated tyrosine. Comparison cytosolic and mitochondrial PheRS from yeast Saccharomyces cerevisiae suggested that organellar protein might lack activity. Yeast was found to contain an site, upon disruption abolished both cis trans Tyr-tRNA(Phe). Wild-type lacked...
Protein synthesis has an overall error rate of approximately 10 -4 for each mRNA codon translated. The fidelity translation is mainly determined by two events: cognate amino acid:tRNA pairs aminoacyl-tRNA synthetases (aaRSs) and accurate selection aminoacyl-tRNAs (aa-tRNAs) the ribosome. To ensure faithful aa-tRNA synthesis, many aaRSs employ a proofreading (“editing”) activity, such as phenylalanyl-tRNA (PheRS) that hydrolyze mischarged Tyr-tRNA Phe . Eukaryotes maintain distinct PheRS...
Aminoacyl-transfer RNA (tRNA) synthetases ligate amino acids to specific tRNAs and are essential for protein synthesis. Although alanyl-tRNA synthetase (AARS) is a implicated in wide range of neurological disorders from Charcot-Marie-Tooth disease infantile epileptic encephalopathy, there have been limited data on their pathogenesis. Here, we report loss-of-function mutations AARS two siblings with progressive microcephaly hypomyelination, intractable epilepsy, spasticity. Whole-exome...
Protein synthesis requires the pairing of amino acids with tRNAs catalyzed by aminoacyl-tRNA synthetases. The synthetases are highly specific, but errors in acid selection occasionally made, opening door to inaccurate translation genetic code. fidelity protein is maintained editing activities synthetases, which remove noncognate from before they delivered ribosome. Although has been described numerous reaction mechanism unknown. To define editing, phenylalanyl-tRNA synthetase was used...
Aminoacyl-tRNA synthetases maintain the fidelity during protein synthesis by selective activation of cognate amino acids at aminoacylation site and hydrolysis misformed aminoacyl-tRNAs editing site. Threonyl-tRNA synthetase (ThrRS) misactivates serine utilizes an cysteine (C182 in Escherichia coli) to hydrolyze Ser-tRNA(Thr). Hydrogen peroxide oxidizes C182, leading Ser-tRNA(Thr) production mistranslation threonine codons as serine. The mechanism C182 oxidation remains unclear. Here we used...
Expansion of the genetic code through engineering translation machinery has greatly increased chemical repertoire proteome. This been accomplished mainly by read-through UAG or UGA stop codons noncanonical aminoacyl-tRNA choice. While codon involves competition with release factors, sense reassignment entails a large pool endogenous tRNAs. We used an engineered pyrrolysyl-tRNA synthetase to incorporate 3-iodo-l-phenylalanine (3-I-Phe) at number different serine and leucine in wild-type...
Significance Protein synthesis is a fundamental cellular process that occurs from bacteria to humans. Highly accurate protein has been shown be critical for the fitness of cell and controlled by sophisticated molecular mechanisms. One such mechanism release mature proteins at stop codons prevent readthrough. Here we identify an environmental stress substantially increases level stop-codon readthrough during in provide insights into underlying mechanism. Intriguingly, fluctuates extensively...
Phenotypic heterogeneity among single cells in a genetically identical population leads to diverse environmental adaptation. The human and animal pathogen Salmonella enterica serovar Typhimurium exhibits heterogeneous expression of virulence genes, including flagellar pathogenicity island (SPI) genes. Little is known about how the differential genes affects bacterial adaptation stresses. Here, we have developed triple-fluorescence reporter simultaneously monitor SPI-1 pathways. We show that...
Translational quality control is monitored at several steps, including substrate selection by aminoacyl-tRNA synthetases (aaRSs), and discrimination of aminoacyl-tRNAs elongation factor Tu (EF-Tu) the ribosome. Phenylalanyl-tRNA synthetase (PheRS) misactivates Tyr but able to correct mistake using a proofreading activity named editing. Previously we found that overproduction editing-defective PheRS resulted in incorporation Phe-encoded positions vivo, although misreading efficiency could not...
Abstract Sense codon recoding is the basis for genetic code expansion with more than two different noncanonical amino acids. It requires an unused (or rarely used) codon, and orthogonal tRNA synthetase:tRNA pair complementary anticodon. The Mycoplasma capricolum genome contains just six CGG arginine codons, without a dedicated Arg . We wanted to reassign this pyrrolysine by providing M. pyrrolysyl‐tRNA synthetase, synthetic CCG anticodon ( ${{\rm tRNA}{{{\rm Pyl}\hfill \atop {\rm...