A5051317898- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Ion channel regulation and function
- Pain Mechanisms and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- bioluminescence and chemiluminescence research
- CRISPR and Genetic Engineering
- Receptor Mechanisms and Signaling
- Pharmacological Effects of Natural Compounds
- Bacterial Genetics and Biotechnology
- RNA regulation and disease
- 3D Printing in Biomedical Research
- Advanced Materials and Mechanics
- Neuroscience and Neural Engineering
- Toxin Mechanisms and Immunotoxins
- Advanced Sensor and Energy Harvesting Materials
- Photosynthetic Processes and Mechanisms
- Protein Structure and Dynamics
- Genomics and Chromatin Dynamics
- Cytokine Signaling Pathways and Interactions
- Neuropeptides and Animal Physiology
- Polyamine Metabolism and Applications
- Hereditary Neurological Disorders
- Connexins and lens biology
University of Wisconsin–Madison
2012-2025
Madison Group (United States)
2024
University of Massachusetts Lowell
2022
The University of Texas at Dallas
2016-2022
Autonomous University of Aguascalientes
2020
Pace University
2020
Carolinas Center for Advanced Management of Pain
2019
University of Arizona
2009-2013
Howard Hughes Medical Institute
2012
Louisiana State University Health Sciences Center New Orleans
2002
Nociceptors rely on cap-dependent translation to rapidly induce protein synthesis in response pro-inflammatory signals. Comparatively little is known regarding the role of regulatory factors bound 3' end mRNA nociceptor sensitization. Poly(A)-binding (PABP) stimulates initiation by bridging Poly(A) tail eukaryotic factor 4F complex associated with cap. Here, we use unbiased assessment PABP binding specificity generate a chemically modified RNA-based competitive inhibitor PABP. The resulting...
The control and function of RNA are governed by the specificity binding proteins. Here, we describe a method for global unbiased analysis RNA-protein interactions that uses in vitro selection, high-throughput sequencing, sequence-specificity landscapes. yields affinities vast array RNAs single experiment, including both low- high-affinity sites. It is reproducible accurate. Using this approach,we analyzed members PUF (Pumilio FBF) family eukaryotic mRNA regulators. Our data identify effects...
Nociceptors, sensory neurons in the DRG that detect damaging or potentially stimuli, are key drivers of neuropathic pain. Injury to these causes activation translation regulation signaling, including mechanistic target rapamycin complex 1 (mTORC1) and mitogen-activated protein kinase interacting (MNK) eukaryotic initiation factor (eIF) 4E pathways. This is a mechanism driving changes excitability nociceptors critical for generation chronic pain states; however, mRNAs translated lead this...
Nociceptors located in the trigeminal ganglion (TG) and DRG are primary sensors of damaging or potentially stimuli for head body, respectively, key drivers chronic pain states. While nociceptors these two tissues show a high degree functional similarity, there important differences their development lineages, connections to CNS, recent genome-wide analyses gene expression suggest that they possess some unique genomic signatures. Here, we used translating ribosome affinity purification...
One of the first signs viral infection is body-wide aches and pain. Although this type pain usually subsides, at extreme, infections can induce painful neuropathies that last for decades. Neither these types sensitization well understood. A key part response to production interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation cellular signaling a variety physiological responses. We sought understand how I IFNs (IFN-α IFN-β) might act...
Baker’s yeast embedded in a hydrogel enables the engineering of smart materials that change shape response to specific cues.
Bacterial luciferase from Vibrio harveyi is a heterodimer composed of catalytic alpha subunit and homologous but noncatalytic beta subunit. Despite decades enzymological investigation, structural evidence defining the active center has been elusive. We report here crystal structure V. bound to flavin mononucleotide (FMN) at 2.3 A. The isoalloxazine ring coordinated by an unusual cis-Ala-Ala peptide bond. reactive sulfhydryl group Cys106 projects toward position C-4a, site oxygenation. This...
Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, neuronal functions. Our results show how specificity one RBP modulated cooperative RNA recognition with a second (Nos) synergistically repress mRNAs. Crystal structures Nos-Pum-RNA reveal that...
Abstract Herein, a method that uses direct‐ink‐write printing to fabricate engineering living materials (ELMs) respond by undergoing programmed shape change in response specific molecules is reported. Stimuli‐responsiveness imparted ELMs integrating genetically engineered yeast only proliferate the presence of biomolecules. This proliferation, turn, leads ELM biomolecule. These are fabricated coprinting bioinks contain multiple strains. Locally, cellular proliferation controllable material...
Abstract Proteins bind and control mRNAs, directing their localization, translation stability. Members of the PUF family RNA-binding proteins multiple mRNAs in a single cell, play key roles development, stem cell maintenance memory formation. Here we identified mRNA targets S. cerevisiae protein, Puf5p, by ultraviolet-crosslinking-affinity purification high-throughput sequencing (HITS-CLIP). The binding sites recognized Puf5p are diverse, with variable spacer lengths between two specific...
Methylglyoxal (MGO) is a reactive glycolytic metabolite associated with painful diabetic neuropathy at plasma concentrations between 500 nM and 5 μM. The mechanisms through which MGO causes neuropathic pain these pathological are not known. Because has been linked to pain, prevalent poorly treated, insight into this unsolved biomedical problem could lead much needed therapeutics. Our experiments provide compelling evidence that ∼1-μM of activate the integrated stress response (ISR) in...
Abstract PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode maintain germline cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1 . Here we report that protein FBF-2 and its LST-1 form a ternary complex represses via pair of adjacent FBF binding elements (FBEs) in 3′UTR. One molecule links two molecules motifs the intrinsically-disordered region; FBE includes well-established ‘canonical’ newly-identified noncanonical FBE....
Abstract Sensory neurons are integral to the genesis and maintenance of neuropathic pain. The molecular mechanisms that mediate long-lived changes in their excitability unclear. Here, we leverage functional genomics approaches survey RNA abundance translation dorsal root ganglion from a mouse model paclitaxel-induced We focus specifically on females as paclitaxel is first-line therapy for breast cancer. sequencing data indicate substantially more occur at level (n = 404) than transcription...
The Staufen family consists of proteins that possess double-stranded RNA-binding domains (dsRBDs). Drosophila and mammals regulate mRNA localization, translation, decay. We report analysis in Caenorhabditis elegans, which we have designated STAU-1. focus on its biochemical properties, targets, possible role RNAi. show STAU-1 is expressed as protein at all stages C. elegans development. wild-type, full-length protein, purified from bacteria, binds duplex RNA with high affinity vitro....
RNA-protein interactions permeate biology. Transcription, translation, and splicing all hinge on the recognition of structured RNA elements by RNA-binding proteins. Models are generally limited to short linear motifs structures because vast sequence sampling required access longer elements. Here, we develop an integrated approach that calculates global pairwise interaction scores from in vitro selection high-throughput sequencing. We examine four proteins phage, viral, human origin. Our...
Following inflammation or injury, sensory neurons located in the dorsal root ganglia (DRG) may exhibit increased spontaneous and/or stimulus-evoked activity, contributing to chronic pain. Current treatment options for peripherally mediated pain are highly limited, driving development of cell- tissue-based phenotypic (function-based) screening assays peripheral analgesic and mechanistic lead discovery. Extant often limited by throughput, content, use tumorigenic cell lines, tissue sources...
Abstract Processing bodies (p-bodies) are a prototypical phase-separated RNA-containing granule. Their abundance is highly dynamic and has been linked to translation. Yet, the molecular mechanisms responsible for coordinate control of two processes unclear. Here, we uncover key roles eEF2 kinase (eEF2K) in ribosome availability p-body abundance. eEF2K acts on sole known substrate, eEF2, inhibit We find that agonist nelfinavir abolishes p-bodies sensory neurons impairs To probe latter, used...
Unlike the vast majority of flavoenzymes, bacterial luciferase requires an exogenous source reduced flavin mononucleotide for bioluminescence activity. Within bioluminescent cells, species-specific oxidoreductases are believed to provide The in Escherichia coli-expressing is not known. There two candidate proteins potentially involved this process E. coli, a homolog Vibrio harveyi Frp oxidoreductase, NfsA, and luxG type Fre. Using single gene knock-out strains, we show that deletion fre...
mRNA control hinges on the specificity and affinity of proteins for their RNA binding sites. Regulatory must bind own sites reject even closely related noncognate In PUF [Pumilio fem-3 factor (FBF)] family proteins, individual discriminate differences in length sequence sites, allowing each to a distinct battery mRNAs. Here, we show that despite these differences, pattern interactions is conserved among proteins: two ends protein make critical contacts with Despite this "two-handed"...