A5033469228- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Telomeres, Telomerase, and Senescence
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Muscle Physiology and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced biosensing and bioanalysis techniques
- Cancer therapeutics and mechanisms
- Toxic Organic Pollutants Impact
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
National Institute on Aging
2016-2025
National Institutes of Health
2016-2025
Institute on Aging
2016-2025
University of Baltimore
2023
Institut thématique Génétique, génomique et bioinformatique
2022-2023
Genomics (United Kingdom)
2022-2023
Government of the United States of America
2022
Howard University
2004-2010
Indian Institute of Technology Kharagpur
2008
North Carolina Central University
2008
Circular RNAs (circRNAs) are widely expressed in animal cells, but their biogenesis and functions poorly understood. CircRNAs have been shown to act as sponges for miRNAs may also potentially sponge RNA-binding proteins (RBPs) thus predicted function robust posttranscriptional regulators of gene expression. The joint analysis large-scale transcriptome data coupled with computational analyses represents a powerful approach elucidate possible biological roles ribonucleoprotein (RNP) complexes....
HuR influences gene expression programs and hence cellular phenotypes by binding to hundreds of coding noncoding linear RNAs. However, whether binds circular RNAs (circRNAs) impacts on their function is unknown. Here, we have identified en masse circRNAs in human cervical carcinoma HeLa cells. One the most prominent target was hsa_circ_0031288, renamed CircPABPN1 as it arises from PABPN1 pre-mRNA. Further analysis revealed that did not influence abundance; interestingly, however, high levels...
A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided cost-effective assembly the genome sequence domestic turkey (Meleagris gallopavo). Heterozygosity sequenced source allowed discovery more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, current (∼1.1 Gb) includes 917 Mb assigned to specific chromosomes. Annotation identified nearly 16,000 genes, 15,093 recognized as protein...
Aging | doi:10.18632/aging.100603. Nicole Noren Hooten, Megan Fitzpatrick, William H. Wood, Supriyo De, Ngozi Ejiogu, Yongqing Zhang, Julie A. Mattison, Kevin G. Becker, Alan B. Zonderman, Michele K. Evans
Abstract Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage signaling from activated oncogenes. At present, senescent cells are identified by the combined presence multiple traits, such as senescence-associated protein expression secretion, DNA β-galactosidase activity; unfortunately, these traits neither exclusively nor universally present cells. To identify robust shared markers we have...
Using RNA sequencing (RNA-Seq), we compared the expression patterns of circular RNAs in proliferating (early-passage) and senescent (late-passage) human diploid WI-38 fibroblasts. Among differentially expressed senescence-associated circRNAs (which termed 'SAC-RNAs'), identified CircPVT1, generated by circularization an exon PVT1 gene, as a showing markedly reduced levels Reducing CircPVT1 fibroblasts triggered senescence, determined rise β-galactosidase activity, higher abundance CDKN1A/P21...
Some mitochondrial long noncoding RNAs (lncRNAs) are encoded by nuclear DNA, but the mechanisms that mediate their transport to mitochondria poorly characterized. Using affinity RNA pull-down followed mass spectrometry analysis, we found two RNA-binding proteins (RBPs), HuR (human antigen R) and GRSF1 (G-rich sequence-binding factor 1), associated with DNA-encoded lncRNA RMRP mobilized it mitochondria. In cultured human cells, bound in nucleus mediated its CRM1 (chromosome region maintenance...
High-throughput RNA sequencing methods coupled with specialized bioinformatic analyses have recently uncovered tens of thousands unique circular (circ)RNAs, but their complete sequences, genes origin and functions are largely unknown. Given that circRNAs lack free ends thus relatively stable, association microRNAs (miRNAs) RNA-binding proteins (RBPs) can influence gene expression programs. While exoribonuclease treatment is widely used to degrade linear RNAs enrich in samples, it does not...
Noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, a wide range of long noncoding (lncRNAs). Although many lncRNAs have been identified, only number characterized functionally. Here, we sought to identify differentially expressed during replicative senescence. We compared in proliferating, early-passage, 'young' human diploid WI-38 fibroblasts [population doubling (PDL) 20] with those senescent, late-passage, 'old' (PDL 52) by RNA sequencing (RNA-Seq)....
The function of the vast majority mammalian long noncoding (lnc) RNAs remains unknown. Here, analysis a highly abundant lncRNA, OIP5-AS1, known as cyrano in zebrafish, revealed that OIP5-AS1 reduces cell proliferation. In human cervical carcinoma HeLa cells, RNA-binding protein HuR, which enhances proliferation, associated with and stabilized it. Tagging MS2 hairpins to identify microRNAs miR-424 interacted competed HuR for binding OIP5-AS1. We further identified 'sponge' high levels...
Abstract Background The genetic contributions to human common disorders and mouse models of disease are complex often overlapping. In diseases, unlike classical Mendelian disorders, factors generally have small effect sizes, multifactorial, highly pleiotropic. Likewise, pleiotropic overlapping phenotypes. Moreover, phenotypic descriptions in the literature both poorly characterized difficult compare directly. Methods this report, association results from summarized with regard replication,...
Aging | doi:10.18632/aging.100834. Kotb Abdelmohsen, Amaresh C. Panda, Supriyo De, Ioannis Grammatikakis, Jiyoung Kim, Jun Ding, Ji Heon Noh, Kyoung Mi Julie A. Mattison, Rafael de Cabo, Myriam Gorospe
Abstract Age-associated changes in gene expression skeletal muscle of healthy individuals reflect accumulation damage and compensatory adaptations to preserve tissue integrity. To characterize these changes, RNA was extracted sequenced from biopsies collected 53 (22–83 years old) the GESTALT study National Institute on Aging–NIH. Expression levels 57,205 protein-coding non-coding RNAs were studied as a function aging by linear negative binomial regression models. From both models, 1134...
Abstract By interacting with proteins and nucleic acids, the vast family of mammalian circRNAs is proposed to influence many biological processes. Here, RNA sequencing analysis differentially expressed during myogenesis revealed that circSamd4 expression increased robustly in mouse C2C12 myoblasts differentiating into myotubes. Moreover, silencing circSamd4, which conserved between human mouse, delayed lowered myogenic markers cultured from both species. Affinity pulldown followed by mass...
Mammalian circRNAs can influence different cellular processes by interacting with proteins and other nucleic acids. Here, we used ribonucleoprotein immunoprecipitation (RIP) analysis to identify systematically the associated cancer-related protein AUF1. Among AUF1 in HeLa (human cervical carcinoma) cells, focused on hsa_circ_0032434 (circPCNX), an abundant target of Overexpression circPCNX specifically interfered binding p21 (CDKN1A) mRNA, thereby promoting mRNA stability elevating...
Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing toward distinct subpopulations. The subpopulations reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis with unsupervised clustering, we found 11 macrophage clusters male mouse SKM enriched gene expression programs linked to reparative, proinflammatory, phagocytic, proliferative,...
Cells responding to DNA damage implement complex adaptive programs that often culminate in one of two distinct outcomes: apoptosis or senescence. To systematically identify factors driving each response, we analyzed human IMR-90 fibroblasts exposed increasing doses the genotoxin etoposide and identified SRC as a key kinase contributing early this dichotomous decision. was activated by low but not high levels etoposide. With damage, SRC-mediated activation p38 critically promoted expression...
Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as model and extending to other quiescent tissues, we find that is driven by temporal chromatin promote refractory cellular state compromise identity. Using an integrated multi-omics approach the first direct visualization chromatin, globally, old cells show H3K27me3-driven broad heterochromatinization transcriptional suppression. At local level,...
Aging | doi:10.18632/aging.204666. Noah Wechter, Martina Rossi, Carlos Anerillas, Dimitrios Tsitsipatis, Yulan Piao, Jinshui Fan, Jennifer L. Martindale, Supriyo De, Krystyna Mazan-Mamczarz, Myriam Gorospe
Few effective therapies exist to improve lower extremity muscle pathology and mobility loss due peripheral artery disease (PAD), in part because mechanisms associated with functional impairment remain unclear. To better understand of PAD, we performed in-depth transcriptomic proteomic analyses on gastrocnemius biopsies from 31 PAD participants (mean age, 69.9 years) 29 age- sex-matched non-PAD controls 70.0 free diabetes or limb-threatening ischemia. Transcriptomic suggested activation...
Cockayne syndrome is a neurodegenerative accelerated aging disorder caused by mutations in the CSA or CSB genes. Although pathogenesis of has remained elusive, recent work implicates mitochondrial dysfunction disease progression. Here, we present evidence that loss neuroblastoma cell line converges on defects ribosomal DNA transcription and activation damage sensor poly-ADP ribose polymerase 1 (PARP1). Indeed, inhibition leads to number lines. Furthermore, machine-learning algorithms predict...
Early B cell development is characterized by large-scale Igh locus contraction prior to V(D)J recombination facilitate a highly diverse Ig repertoire. However, an understanding of the molecular architecture that mediates remains unclear. We have combined high-resolution chromosome conformation capture (3C) techniques with 3D DNA FISH identify three conserved topological subdomains. Each these folds encompasses major VH gene family become juxtaposed in pro-B cells via megabase-scale chromatin...