A5007511847- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Circadian rhythm and melatonin
- Viral Infections and Immunology Research
- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Cancer-related gene regulation
- Cardiac Arrest and Resuscitation
- Pluripotent Stem Cells Research
- Sleep and Wakefulness Research
- Liver Disease and Transplantation
- Neuroendocrine regulation and behavior
- Bacterial Genetics and Biotechnology
- Renal function and acid-base balance
- Molecular Biology Techniques and Applications
- DNA and Nucleic Acid Chemistry
- Reproductive Biology and Fertility
- Stress Responses and Cortisol
- Biochemical effects in animals
Washington University in St. Louis
2014-2019
Simon Fraser University
2010
Brigham and Women's Hospital
2000
Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle the translational apparatus; however, effects of damaged mRNA on speed accuracy decoding process their interplay with quality-control processes are not known. Here, we systematically explore oxidative using well-defined bacterial in vitro translation system. We find that lesion 8-oxoguanosine (8-oxoG) reduces rate peptide-bond formation by more than three orders magnitude independent position...
Oxidation and alkylation of nucleobases are known to disrupt their base-pairing properties within RNA. It is, however, unclear whether organisms have evolved general mechanism(s) deal with this damage. Here we show that the mRNA-surveillance pathway no-go decay associated ribosome-quality control activated in response nucleobase oxidation. Our findings reveal these processes important for clearing chemically modified mRNA resulting aberrant-protein products. In absence Xrn1, level damaged...
In mammals, the suprachiasmatic nucleus (SCN) of hypothalamus coordinates daily rhythms including sleep–wake, hormone release, and gene expression. The cells SCN must synchronize to each other drive these circadian in rest body. ontogeny cycling intercellular coupling remains poorly understood. Recent vitro studies have recorded from whole embryonic SCN. Here, we tracked onset precision PERIOD2 (PER2), a clock protein, within isolated postnatal mice undetermined sex. We found that few...
During translation, an mRNA is typically occupied by multiple ribosomes sparsely distributed across the coding sequence. This distribution, mediated slow rates of initiation relative to elongation, ensures that they rarely collide with each other, but given stochastic nature protein synthesis, collision events do occur. Recent work from our lab suggested collisions signal for degradation through no-go decay (NGD). We have explored impact stalling on ribosome function when NGD compromised and...
Termination of protein synthesis on the ribosome is catalyzed by release factors (RFs), which share a conserved glycine-glycine-glutamine (GGQ) motif. The glutamine residue methylated in vivo, but mechanistic understanding its contribution to hydrolysis lacking. Here, we show that modification, apart from increasing overall rate termination all dipeptides, substantially increases peptide subset amino acids. In presence unmethylated RFs, measure rates are exceptionally slow proline and...
The suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behavior. Previous studies suggest a critical role for neurons expressing vasoactive intestinal peptide (VIP) coordinating rhythmicity synchronization the SCN. Here we examined firing properties of VIP-expressing SCN acute brain slices. Active passive membrane were measured VIP non-VIP during day at night. Current-clamp recordings revealed that both spontaneously active, with higher rates than Average frequencies,...
No-go Decay (NGD) is a process that has evolved to deal with stalled ribosomes resulting from structural blocks or aberrant mRNAs. The distinguished by an endonucleolytic cleavage prior degradation of the transcript. While many details pathway have been described, identity endonuclease remains unknown. Here we identify residues small subunit ribosomal protein Rps3 are important for NGD affecting reaction. Mutation within entry tunnel contact incoming mRNA leads significantly reduced...
Of the four bases, guanine is most susceptible to oxidation, which results in formation of 8-oxoguanine (8-oxoG). In protein-free DNA, 8-oxodG adopts syn conformation more frequently than anti one. conformation, base pairs with dA. The equilibrium between and conformations adduct are known be altered by enzyme recognizing 8-oxodG. We previously showed that 8-oxoG mRNA severely disrupts tRNA selection, but underlying mechanism for these effects was not addressed. Here, we use miscoding...
Nucleic acids are constantly under assault from both endogenous and exogenous agents that can affect their chemical properties hence function. These assaults include reactive oxygen species (ROS), ultraviolet light alkylating agents. ROS present normal conditions as byproducts metabolic reactions. Furthermore, oxidative stress, levels increase significantly. In contrast to DNA, damaged RNA has received little attention presumably due its transient nature. My laboratory is currently...