A5062087832- RNA Research and Splicing
- RNA modifications and cancer
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Telomeres, Telomerase, and Senescence
- RNA and protein synthesis mechanisms
- Circular RNAs in diseases
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- Ocular Surface and Contact Lens
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Salivary Gland Disorders and Functions
- Vector-borne infectious diseases
- Pituitary Gland Disorders and Treatments
- Cellular transport and secretion
- Olfactory and Sensory Function Studies
- PI3K/AKT/mTOR signaling in cancer
- Erythrocyte Function and Pathophysiology
- Endoplasmic Reticulum Stress and Disease
- Molecular Biology Techniques and Applications
- Metabolism, Diabetes, and Cancer
- Mosquito-borne diseases and control
Government Medical College and Hospital
2024
The University of Texas Health Science Center at San Antonio
2013-2022
The University of Texas Health Science Center at Houston
2020
National Institutes of Health
2008-2014
National Institute on Aging
2008-2013
Council of Scientific and Industrial Research
2010-2013
Centre for Cellular and Molecular Biology
2005-2013
MRC Laboratory of Molecular Biology
2011-2012
University of Baltimore
2011
Institute on Aging
2009-2011
RNA-binding proteins (RBPs) and microRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. Here, we show that the RBP HuR reduced c-Myc expression by associating with 3′ untranslated region (UTR) next to a miRNA let-7-binding site. Lowering or let-7 levels relieved translational repression c-Myc. Unexpectedly, repressed through an interdependent mechanism, as required reduce inhibit Our findings suggest regulatory paradigm wherein inhibits recruiting let-7-loaded RISC...
Adipose tissue development is tightly regulated by altering gene expression.MicroRNAs are strong posttranscriptional regulators of mammalian differentiation.We hypothesized that microRNAs might influence human adipogenesis targeting specific adipogenic factors.We identified showed varying abundance during the differentiation preadipocytes into adipocytes.Among them, miR-130 strongly affected adipocyte differentiation, as overexpressing impaired and reducing enhanced adipogenesis.A key...
Background Expression of the tumor suppressor p16INK4a increases during aging and replicative senescence. Methodology/Principal Findings Here, we report that microRNA miR-24 suppresses p16 expression in human diploid fibroblasts cervical carcinoma cells. Increased with senescence was associated decreased levels miR-24, a predicted to associate mRNA coding 3′-untranslated regions. Ectopic overexpression reduced protein but not levels. Conversely, introduction antisense (AS)-miR-24 blocked...
Gene expression is potently regulated through the action of RNA-binding proteins (RBPs) and microRNAs (miRNAs). Here, we present evidence a miRNA regulating an RBP. The RBP HuR can stabilize modulate translation numerous target mRNAs involved in cell proliferation, but little known about mechanisms that regulate abundance. We identified two putative sites miR-519 interaction on mRNA, one its coding region (CR), 3'-untranslated (UTR). In several human carcinoma lines tested, HeLa (cervical),...
A predominantly nuclear RNA-binding protein, HuR translocates to the cytoplasm in response stress and proliferative signals, where it stabilizes or modulates translation of target mRNAs. Here, we present evidence that phosphorylation at S202 by G2-phase kinase Cdk1 influences its subcellular distribution. was specifically phosphorylated synchronous cultures; cytoplasmic levels increased Cdk1-inhibitory interventions declined Cdk1-activating interventions. In keeping with prominently location...
Mitochondrial Ca2+ (mCa2+) uptake mediated by the mitochondrial calcium uniporter (MCU) plays a critical role in signal transduction, bioenergetics, and cell death, its dysregulation is linked to several human diseases. In this study, we report new ruthenium complex Ru265 that cell-permeable, minimally toxic, highly potent with respect MCU inhibition. Cells treated show inhibited activity without any effect on cytosolic dynamics membrane potential (ΔΨm). Dose-dependent studies reveal more...
MicroRNAs (miRNAs) are short non-coding RNAs that regulate diverse biological processes by controlling the pattern of expressed proteins. In mammalian cells, miRNAs partially complement their target sequences leading to mRNA degradation and/or decreased translation. Here, we have analyzed transcriptome-wide changes in senescent relative early-passage WI-38 human diploid fibroblasts (HDFs). Among downregulated with senescence were members let-7 family, while upregulated included miR-1204,...
RNA-binding proteins (RBPs) regulate gene expression at many post-transcriptional levels, including mRNA stability and translation. The RBP nucleolin, with four RNA-recognition motifs, has been implicated in cell proliferation, carcinogenesis viral infection. However, the subset of nucleolin target mRNAs influence on their had not studied a transcriptome-wide level. Here, we globally identified transcripts, which encoded growth- cancer-related proteins, used them to find signature motif...
Neuronal development and plasticity are maintained by tightly regulated gene expression programs. Here, we report that the developmentally microRNA miR-375 affects dendrite formation maintenance. overexpression in mouse hippocampus potently reduced density. We identified predominantly neuronal RNA-binding protein HuD as a key effector of influence on Heterologous reporter analysis verified repressed through specific, evolutionarily conserved site 3′ untranslated region. lowered both mRNA...
The RNA-binding protein HuR is highly abundant in many cancers. expression was recently found to be repressed by microRNA miR-519, which potently lowered translation without influencing mRNA abundance. Here, we examined the levels of and miR-519 pairs cancer adjacent healthy tissues from ovary, lung, kidney. In three sample collections, specimens showed dramatically higher levels, unchanged concentrations, markedly reduced when compared with tissues. As tested using human cervical carcinoma...
Pheochromocytomas and paragangliomas are highly vascular tumors of the autonomic nervous system. Germline mutations, including those in hypoxia-related genes, occur one third cases, but somatic mutations infrequent these tumors. Using exome sequencing six paired constitutive tumor DNA from sporadic pheochromocytomas paragangliomas, we identified a mutation HIF2A ( EPAS1 ) gene. Screening an additional 239 pheochromocytomas/paragangliomas uncovered three other variants (4/167, 2.3%) not...
Mitochondrial Ca2+ uniporter (MCU)-mediated uptake promotes the buildup of reducing equivalents that fuel oxidative phosphorylation for cellular metabolism. Although MCU modulates mitochondrial bioenergetics, its function in energy homeostasis vivo remains elusive. Here we demonstrate deletion Mcu gene mouse liver (MCUΔhep) and Danio rerio by CRISPR/Cas9 inhibits (mCa2+) uptake, delays cytosolic (cCa2+) clearance, reduces phosphorylation, leads to increased lipid accumulation. Elevated...
Significance The assembly and function of membrane proteins depend on the lipid milieu. In recent years protein components mitochondrial calcium uniporter have been identified, but its specific phospholipid requirements are not known. Utilizing yeast mutants defective in their ability to synthesize different phospholipids, we identify a requirement cardiolipin (CL) stability uniporter. Our findings translatable higher organisms because endogenous abundance is decreased patient-derived cells...
SARS-CoV-2 is a newly identified coronavirus that causes the respiratory disease called 2019 (COVID-19). With an urgent need for therapeutics, we lack full understanding of molecular basis SARS-CoV-2-induced cellular damage and progression. Here, conducted transcriptomic analysis human PBMCs, significant changes in mitochondrial, ion channel, protein quality-control gene products. proteins selectively target organelle compartments, including endoplasmic reticulum mitochondria. M-protein,...
The RNA-binding protein (RBP) nucleolin promotes the expression of several proliferative proteins. Nucleolin levels are high in cancer cells, but mechanisms that control unknown. Here, we show abundance is controlled posttranscriptionally via factors associate with its 3' untranslated region (3'UTR). RBP HuR was found to interact (NCL) 3'UTR and specifically promoted translation without affecting mRNA levels. In human cervical carcinoma HeLa analysis a traceable NCL bearing MS2 RNA hairpins...