A5016501132- RNA Research and Splicing
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
- Viral Infections and Vectors
- interferon and immune responses
- HIV Research and Treatment
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Burkholderia infections and melioidosis
- Invertebrate Immune Response Mechanisms
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- Antibiotic Resistance in Bacteria
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Bee Products Chemical Analysis
- Clinical practice guidelines implementation
- Viral Infectious Diseases and Gene Expression in Insects
- Click Chemistry and Applications
- Animal Disease Management and Epidemiology
- Advanced Electron Microscopy Techniques and Applications
- Toxin Mechanisms and Immunotoxins
University of Michigan
2020-2025
Rural Development Administration
2025
National Academy of Agricultural Science
2025
Center for Human Genetics
2023
Oregon State University Cascades
2020
University of Colorado Boulder
2018-2019
Colorado State University
2012-2015
Flaviviruses are emerging human pathogens and worldwide health threats. During infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) produced by resisting degradation the 5'→3' host cell exonuclease Xrn1 through an unknown RNA structure-based mechanism. Here, we present crystal structure of a complete Xrn1-resistant RNA, which contains interwoven pseudoknots within compact that depends on highly conserved nucleotides. The RNA's three-dimensional topology creates ringlike conformation,...
Dengue virus is a growing global health threat. and other flaviviruses commandeer the host cell’s RNA degradation machinery to generate small flaviviral (sfRNA), noncoding that induces cytopathicity pathogenesis. Host cell exonuclease Xrn1 likely loads on 5′ end of viral genomic degrades processively through ∼10 kB RNA, halting near 3′ RNA. The surviving sfRNA. We interrogated architecture complete 2 sfRNA, identifying five independently-folded structures, two which quantitatively confer...
All arthropod-borne flaviviruses generate a short noncoding RNA (sfRNA) from the viral 3′ untranslated region during infection due to stalling of cellular 5′-to-3′ exonuclease XRN1. We show here that formation sfRNA also inhibits XRN1 activity. Cells infected with Dengue or Kunjin viruses accumulate uncapped mRNAs, decay intermediates normally targeted by repression resulted in increased overall stability mRNAs flavivirus-infected cells. Importantly, mutant virus cannot form but replicates...
We demonstrate that both Hepatitis C virus (HCV) and Bovine Viral Diarrhea (BVDV) contain regions in their 5' UTRs stall repress the enzymatic activity of cellular 5'-3' exoribonuclease XRN1, resulting dramatic changes stability mRNAs. used biochemical assays, infections, transfection HCV BVDV untranslated absence other viral gene products to directly existence mechanism this novel host-virus interaction. In context infection, we observed globally increased mRNAs significant increases...
Highlights•Sindbis virus 3′ UTR acts as a sponge for the cellular HuR protein•HuR-mediated mRNA stability is dysregulated upon Sindbis infection•HuR-regulated alternative splicing and polyadenylation are altered by virus•Sequestration of proteins viral RNAs can disrupt posttranscriptional controlSummaryThe impact RNA viruses on regulation gene expression unclear. causes dramatic relocalization protein from nucleus to cytoplasm in infected cells. This result large amounts that contain...
Stress granules are dynamic assemblies of proteins and nontranslating RNAs that form when translation is inhibited in response to diverse stresses. Defects ubiquitin–proteasome system factors including valosin-containing protein (VCP) the proteasome impact kinetics stress granule induction dissolution as well being implicated neuropathogenesis. However, impacts dysregulated proteostasis on mRNA regulation not understood. Using single imaging, we discovered ribosomes stall some mRNAs during...
Mutations in eIF2B genes cause vanishing white matter disease (VWMD), a fatal leukodystrophy that can manifest following physical trauma or illness, conditions activate the integrated stress response (ISR). EIF2B is guanine exchange factor for eIF2, facilitating ternary complex formation and translation initiation. During ISR, eIF2α phosphorylated inhibits eIF2B, causing global suppression stress-induced gene translation, allowing adaptation recovery. We demonstrate VWMD patient cells...
To combat influenza A virus (IAV) infection, it is vital to develop effective therapeutic strategies, including immunomodulators. In this study, we examined the antiviral effects of Hovenia dulcis Thunb. honey (HDH) against IAV using RAW 264.7 cells. HDH treatment significantly reduced infection and viral protein expression. Moreover, enhanced production interferon (IFN)-β, activated innate immune response through cyclic GMP-AMP synthase (cGAS)-stimulator genes (STING) pathway, upregulated...
In response to stress, translation initiation is suppressed and ribosome runoff via elongation drives mRNA assembly into ribonucleoprotein (RNP) granules including stress P-bodies. Defects in activate the integrated response. If how stalled ribosomes are removed from mRNAs during drive RNP granule not clear. We demonstrate induced upon tRNA synthetase inhibition part collision sensing. However, saturating levels of inhibitors do induce or P-bodies prevent exogenous stress. The loss activity...
Eukaryotic cells respond to stress and changes in the environment part by repressing translation forming cytoplasmic assemblies called granules P-bodies, which harbor non-translating mRNAs proteins. A third, but poorly understood, assembly eIF2B body can form contains complex, an essential guanine exchange factor for initiation eIF2. Hypomorphic EIF2B alleles lead Vanishing White Matter Disease (VWMD), a leukodystrophy that causes progressive white matter loss. An unexplored question is how...
The bacterium Burkholderia thailandensis produces an arsenal of secondary metabolites that have diverse structures and roles in the ecology this soil-dwelling bacterium. In coculture experiments, B. strain E264 secretes antimicrobial nearly eliminates another soil bacterium, Bacillus subtilis 168. To identify antimicrobial, we used a transposon mutagenesis approach. This screen identified antimicrobial-defective mutants with insertions hmqA, hmqC, hmqF genes involved biosynthesis family...
Abstract During cellular stress mRNAs exit translation and accumulate in granules P-bodies, although the dynamics of these interactions remain unclear. We imaged real-time single mRNAs, their translational output, mRNA-granule during stress. observed interacting with moving bidirectionality between them. While translating only interact RNP dynamically, non-translating can form stable associations that rigidly immobilize mRNA within granule. Imaging thousands individual showed probability...