A5035595630- RNA Research and Splicing
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Circular RNAs in diseases
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Neurobiology and Insect Physiology Research
- Skin Protection and Aging
- Nerve injury and regeneration
- RNA regulation and disease
- Adipose Tissue and Metabolism
- Invertebrate Immune Response Mechanisms
- Insect symbiosis and bacterial influences
- Viral Infections and Immunology Research
- Sirtuins and Resveratrol in Medicine
- Signaling Pathways in Disease
- Cancer-related gene regulation
- bioluminescence and chemiluminescence research
- Peroxisome Proliferator-Activated Receptors
- Insect Utilization and Effects
- Biotin and Related Studies
- Protein Degradation and Inhibitors
- Immune cells in cancer
University of Nevada, Reno
2016-2025
Tulane University
2024
Okinawa Institute of Science and Technology Graduate University
2024
UConn Health
2023
University of Connecticut
2023
Kettering University
2011-2020
University of Ottawa
2005-2013
Concordia University
2007
Ottawa Hospital
2007
University of Notre Dame
2002
Highlights•Fly circular RNAs were annotated from >100 libraries and >10 billion total RNA-seq reads•Circular RNA properties include strong preference for long flanking introns•Circular are strongly biased to contain coding region conserved miRNA sites•Circular dominantly accumulate in the nervous system increase with ageSummaryCircularization was recently recognized broadly expand transcriptome complexity. Here, we exploit massive Drosophila RNA-sequencing data, >5 paired-end reads covering...
Remarkable advances in techniques for gene expression profiling have radically changed our knowledge of the transcriptome. Recently, mammalian brain was reported to express many long intergenic noncoding (lincRNAs) from loci downstream protein-coding genes. Our experimental tests failed validate specific accumulation lincRNA transcripts, and instead revealed strongly distal 3′ UTRs generated by alternative cleavage polyadenylation (APA). With this perspective mind, we analyzed deep RNA-seq...
Abstract Circular RNAs (circRNAs) are a newly appreciated class of expressed across diverse phyla. These enigmatic transcripts most commonly generated by back-splicing events from exons protein-coding genes. This results in highly stable due to the lack free 5′ and 3′ ends. CircRNAs enriched neural tissues, suggesting that they might have functions. Here, we sought determine whether circRNA accumulation occurs during aging mice. Total RNA-seq profiling young (1 month old) aged (22 cortex,...
We analyzed the usage and consequences of alternative cleavage polyadenylation (APA) in Drosophila melanogaster by using >1 billion reads stranded mRNA-seq across a variety dissected tissues. Beyond demonstrating that majority fly transcripts are subject to APA, we observed broad trends for 3' untranslated region (UTR) shortening testis lengthening central nervous system (CNS); latter included hundreds unannotated extensions ranging up 18 kb. Extensive northern analyses validated...
A subset of microtubule-associated proteins, including cytoplasmic linker protein (CLIP)-170, dynactin, EB1, adenomatous polyposis coli, dynein, CLASPs, and LIS-1, has been shown recently to target the plus ends microtubules. The mechanisms functions this binding specificity are not understood, although a role in encouraging microtubule elongation proposed. To extend previous work on dynactin organelle transport, we analyzed p150Glued by live-cell imaging. Time-lapse analysis revealed...
Neuromuscular junction degeneration is a prominent aspect of sarcopenia, the age-associated loss skeletal muscle integrity. Previously, we showed that stem cells activate and contribute to mouse neuromuscular regeneration in response denervation (Liu et al., 2015). Here, examined gene expression profiles integrity aged muscles, unexpectedly found limited despite high level degenerated junctions. Instead, junctions were associated with reduced contribution from cells. Indeed, cell depletion...
Circular RNAs (CircRNAs) are a newly appreciated class of that lack free 5′ and 3′ ends, expressed by the thousands in diverse forms life, mostly enigmatic function. Ostensibly due to their resistance exonucleases, circRNAs known be exceptionally stable. Previous work Drosophila mice have shown increase during aging neural tissues. Here, we examined global profile C. elegans performing ribo-depleted total RNA-seq from fourth larval stage (L4) through 10-day old adults. Using stringent...
A therapeutic approach for Duchenne muscular dystrophy (DMD) is to up-regulate utrophin in skeletal muscle an effort compensate the lack of dystrophin. We previously hypothesized that promotion slow, oxidative myogenic program, which triggers up-regulation, can attenuate dystrophic pathology mdx animals. Since treatment healthy mice with AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) enhances capacity and elicits a fast-to-slow...
Abstract Circular RNAs (circRNAs) are highly expressed in the brain and their expression increases during neuronal differentiation. The factors regulating circRNAs developing mouse unknown. NOVA1 NOVA2 neural-enriched RNA-binding proteins with well-characterized roles alternative splicing. Profiling of from RNA-seq data revealed that global circRNA levels were reduced embryonic cortex Nova2 but not Nova1 knockout mice. Analysis isolated inhibitory excitatory cortical neurons lacking an even...
A therapeutic strategy to treat Duchenne muscular dystrophy (DMD) involves identifying compounds that can elevate utrophin expression in muscle fibers of affected patients. The dystrophin homologue functionally substitute for when its levels are enhanced the mdx mouse model DMD. Utrophin skeletal is regulated by mechanisms promote slow myofiber program. Since activation peroxisome proliferator-activated receptor (PPAR) beta/delta promotes oxidative phenotype muscle, we initiated studies...
Brain-derived neurotrophic factor (BDNF) is required for efficient skeletal-muscle regeneration and perturbing its expression causes abnormalities in the proliferation differentiation of skeletal muscle cells. In this study, we investigated mechanism BDNF suppression that occurs during myogenic differentiation. expressed at mRNA level as two isoforms differ length their 3'UTRs a result alternative cleavage polyadenylation. Sequence analysis revealed presence three miR-206 target sites long...
Aging is associated with functional decline of neurons and increased incidence both neurodegenerative ocular disease. Photoreceptor in Drosophila melanogaster provide a powerful model for studying the molecular changes involved senescence since decreased visual behavior precedes retinal degeneration. Here, we sought to identify gene expression genomic features differentially regulated genes photoreceptors that contribute senescence.To could lead senescence, characterized aging transcriptome...
Major applications of RNA-seq data include studies how the transcriptome is modulated at levels gene expression and RNA processing, these events are related to cellular identity, environmental condition, and/or disease status. While many excellent tools have been developed analyze data, generally limited efficacy for annotating 3' UTRs. Existing assembly strategies often fragment long UTRs, importantly, none algorithms in popular use can apportion into tandem UTR isoforms, which frequently...
Many metazoan genes express alternative long 3′ UTR isoforms in the nervous system, but their functions remain largely unclear. In Drosophila melanogaster, Dscam1 gene generates short and (Dscam1-L) because of polyadenylation (APA). Here, we found that RNA-binding protein Embryonic Lethal Abnormal Visual System (Elav) impacts biogenesis at two levels, including regulation skipping an upstream exon (exon 19). MinION long-read sequencing confirmed connectivity this splicing event to UTR....
Abstract Nervous system development is associated with extensive regulation of alternative splicing (AS) and polyadenylation (APA). AS APA have been extensively studied in isolation, but little known about how these processes are coordinated. Here, the coordination cassette exon (CE) Drosophila was investigated using a targeted long-read sequencing approach we call Pull-a-Long-Seq (PL-Seq). This cost-effective method uses cDNA pulldown Nanopore combined an analysis pipeline to quantify...
Herbivorous insects tolerate chemical and metabolic variation in their host plant diet by modulating physiological traits. Insect immune response is one such trait that plays a crucial role maintaining fitness but can be heavily influenced quality. An important question how the use of different plants affects ability herbivorous to resist viral pathogens. Furthermore, transcriptional changes associated with this interaction pathogens remain understudied. The Melissa blue butterfly (Lycaeides...
The majority of mouse and human genes are subject to alternative cleavage polyadenylation (APA), which most often leads the expression two or more length 3′ untranslated region (3′-UTR) mRNA isoforms. In neural tissues, there is enhanced APA isoforms with longer 3′-UTRs on a global scale, but physiological relevance these 3′-UTR poorly understood. Calmodulin 1 ( Calm1) key integrator calcium signaling that generates short Calm1-S ) long Calm1-L via APA. We found be largely restricted tissues...
Utrophin up-regulation in muscle fibers of Duchenne muscular dystrophy patients represents a potential therapeutic strategy. It is thus important to delineate the regulatory events presiding over utrophin attempts develop pharmacological interventions aimed at increasing expression. A number studies have now shown that under several experimental conditions, abundance increased without corresponding elevation its mRNA. Here, we examine whether expression regulated translational level...