A5080225235- RNA modifications and cancer
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- Herpesvirus Infections and Treatments
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Mine drainage and remediation techniques
- RNA Interference and Gene Delivery
- HVDC Systems and Fault Protection
- Neurogenetic and Muscular Disorders Research
- COVID-19 Clinical Research Studies
- Microtubule and mitosis dynamics
- Fungal and yeast genetics research
- Molecular Biology Techniques and Applications
- Photodynamic Therapy Research Studies
- SARS-CoV-2 and COVID-19 Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Extracellular vesicles in disease
- Acne and Rosacea Treatments and Effects
Case Western Reserve University
2011-2024
University School
2022
Cleveland Clinic Lerner College of Medicine
2016-2020
Cleveland Clinic
2017
Ohio University
2006-2007
Northeast Ohio Medical University
2006-2007
Coupling translation and mRNA decay Gene expression requires messenger RNAs (mRNAs)—DNA-derived blueprints of genes—to be translated by protein-producing ribosomes. The levels mRNAs are tightly regulated, in part controlling their half-lives. In eukaryotic cells, half-life is largely linked to translational efficiency, but the mechanism underlying this link has remained elusive. Buschauer et al. used cryo–electron microscopy RNA sequencing show how a key regulator degradation, Ccr4-Not...
Transfer RNAs (tRNA) are quintessential in deciphering the genetic code; disseminating nucleic acid triplets into correct amino identity. While this decoding function is clear, an emerging theme that tRNA abundance and functionality can powerfully impact protein production rate, folding, activity, messenger RNA stability. Importantly, however, expression pattern of tRNAs obliquely known. Here we present Quantitative Mature sequencing (QuantM-tRNA seq), a technique to monitor sequence...
Translational control and messenger RNA (mRNA) decay represent important points in the regulation of gene expression. In yeast, major pathway for mRNA is initiated by deadenylation followed decapping 5'-3' exonucleolytic digestion mRNA. Proteins that activate decapping, such as DEAD-box helicase Dhh1, have been postulated to function limiting translation initiation, thereby promoting a ribosome-free targeted decapping. contrast this model, we show here Dhh1 represses vivo at step subsequent...
Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels the cell and is major control point for modulating gene expression. In yeast other model organisms, codon identity powerful determinant of stability, contributing broadly to impact half-lives. General principles governing mRNA stability are poorly understood mammalian systems. Importantly, however, machinery highly conserved, thus it seems logical that half-lives would also be strongly influenced by coding...
Abstract In late 2019, a novel coronavirus named severe acute respiratory syndrome 2 (SARS‐CoV‐2) emerged in Wuhan, China. SARS‐CoV‐2 and the disease it causes, 2019 (COVID‐19), spread rapidly became global pandemic early 2020. spike protein is responsible for viral entry binds to angiotensin converting enzyme (ACE2) on host cells, making major target of immune system – particularly neutralizing antibodies (nAbs) that are induced by infection or vaccines. Extracellular vesicles (EVs) small...
The RNA binding protein DAZL is essential for gametogenesis, but its direct in vivo functions, targets, and the molecular basis germ cell loss Dazl-null mice are unknown. Here, we mapped transcriptome-wide DAZL-RNA interactions vivo, revealing to thousands of mRNAs via polyA-proximal 3′ UTR interactions. In parallel, fluorescence-activated sorting RNA-seq identified sensitive deletion male cells. Despite a broad set mRNAs, integrative analyses indicate that post-transcriptionally controls...
To evaluate the effects of anti-inflammatory hydroxystilbene, resveratrol, on Propionibacterium acnes growth. Three different strains P. were tested against resveratrol at concentrations between 0 and 200 mg/L. Piceatannol was included as a second hydroxystilbene to compare with erythromycin benzoyl peroxide used positive controls. After 24 h treatment average 50% inhibitory concentration (IC50) 73 mg/L 100% (IC100) 187 for three tested. The IC50 IC100 piceatannol 123 234 mg/L, respectively....
Processing bodies (P-bodies) are subcellular ribonucleoprotein (RNP) granules that have been hypothesized to be sites of mRNA degradation, translational control, and/or storage. Importantly, P-bodies conserved from yeast mammals and contain a common set evolutionarily protein constituents. dynamic structures their formation appears fluctuate in correlation with alterations metabolism. Despite these observations, little is understood about how P-body formed within the cell. In this study, we...
RNA binding proteins (RBPs) are increasingly recognized as essential factors in tissue development and homeostasis. The polypyrimidine tract (PTB) protein family of RBPs important posttranscriptional regulators gene expression. In the nervous system, function importance PTB 2 (Ptbp2) a key alternative splicing regulator is well established. Ptbp2 also abundantly expressed during spermatogenesis, but its role this developmental program has not been explored. Additionally, regulation...
Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels eukaryotic cells. Previous work by us and others has shown that codon identity exerts powerful influence on mRNA stability. In Saccharomyces cerevisiae, studies using handful of reporter mRNAs show optimal codons increase translation elongation rate, which turn increases However, direct relationship between rate stability not been established across the entire yeast transcriptome. addition, there is...
Abstract Oligodendrocytes are specialized cells that confer neuronal myelination in the central nervous system. Leukodystrophies associated with oligodendrocyte deficits and hypomyelination known to result when a number of tRNA metabolism genes mutated. Thus, for unknown reasons, oligodendrocytes may be hypersensitive perturbations biology. In this study, we survey transcriptome murine cell lineage find specific tRNAs hypomodified within or near anticodon compared progenitor (OPCs). This...
mRNA degradation is a critical, yet poorly understood, aspect of gene expression. Previous studies demonstrate that codon content acts as major determinant stability in model organisms. In humans, the importance open reading frame (ORF)-mediated regulation remains unclear. Here, we globally analyzed for both endogenous and human ORFeome collection mRNAs cells. Consistent with previous studies, observed synonymous usage impacts decay. Unexpectedly, amino acid identity also driver...
Control of mRNA decay rate is intimately connected to translation elongation but the spatial coordination these events poorly understood. The Ccr4-Not complex initiates through deadenylation and activation decapping. Using a combination cryo-electron microscopy, ribosome profiling stability assays we show recruitment via specific interaction Not5 subunit with ribosomal E-site. This only occurs when lacks accommodated A-site tRNA, indicative low codon optimality. Loss results in inability...
Abstract Transfer RNAs (tRNA) are quintessential in deciphering the genetic code; disseminating nucleic acid triplets into correct amino identity. While this decoding function is clear, an emerging theme that tRNA abundance and functionality can powerfully impact protein production rate, folding, activity, messenger RNA stability. Importantly, however, expression pattern of tRNAs obliquely known. Here we present Quant itative M ature seq uencing (QuantM-tRNA seq), a technique to monitor...
The basis of many life-threatening diseases is disruption in key genes. In cases, repairing these disruptions can prevent or reverse disease. development CRISPR-Cas9 technology, which consists Cas9 nuclease directed to specific genomic locations by guide RNA (gRNA), has significantly progressed the past decade and shown signs promise for treating such as Alzheimer’s cystic fibrosis. One integral issue gene editing therapy method effectiveness delivery. Current approaches lentiviral...