A5053790742- RNA Research and Splicing
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Fungal and yeast genetics research
- DNA Repair Mechanisms
- Curcumin's Biomedical Applications
- Cancer-related Molecular Pathways
- Amyotrophic Lateral Sclerosis Research
- Genetics and Neurodevelopmental Disorders
- 14-3-3 protein interactions
- Neurobiology and Insect Physiology Research
- Plant Molecular Biology Research
Emory University
2011-2023
Yale University
2009-2014
All India Institute of Medical Sciences
2010
Louisiana State University Health Sciences Center New Orleans
2008-2009
The polyadenylate binding protein 1 (PABPN1) is a ubiquitously expressed RNA vital for multiple steps in metabolism. Although PABPN1 plays critical role the regulation of processing, mutation gene encoding this causes specific form muscular dystrophy termed oculopharyngeal (OPMD). Despite tissue-specific pathology that occurs disease, only recently have studies begun to explore skeletal muscle. We used co-immunoprecipitation and mass spectrometry identify proteins interact with mouse...
In Saccharomyces cerevisiae, non-coding RNAs, including cryptic unstable transcripts (CUTs), are subject to degradation by the exosome. The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex in S. cerevisiae is a nuclear exosome cofactor that recruits degrade RNAs. Trf4/5 poly(A) polymerases, Mtr4 an RNA helicase, and Air1/2 putative RNA-binding proteins contain five CCHC zinc knuckles (ZnKs). One central question how TRAMP complex, especially protein, recognizes its substrates. To...
The ZC3H14 gene, which encodes a ubiquitously expressed, evolutionarily conserved, nuclear, zinc finger polyadenosine RNA-binding protein, was recently linked to autosomal recessive, nonsyndromic intellectual disability. Although studies have been carried out examine the function of putative orthologs in Saccharomyces cerevisiae , where protein is termed Nab2, and Drosophila has designated dNab2, little known about mammalian ZC3H14. Work from both budding yeast flies implicates Nab2/dNab2...
Trinucleotide repeat expansion is the genetic basis for a sizeable group of inherited neurological and neuromuscular disorders. Friedreich ataxia (FRDA) relentlessly progressive neurodegenerative disorder caused by GAA·TTC in first intron FXN gene. The expanded reduces mRNA expression length tract proportional to disease severity. Somatic sequence disease-relevant tissues thought contribute progression severity during patient aging. Previous models instability have not been able produce...
Oculopharyngeal muscular dystrophy (OPMD) is a late onset disease caused by polyalanine expansion in the poly(A) binding protein nuclear 1 (PABPN1). Several mouse models have been generated to study OPMD; however, most of these employed transgenic overexpression alanine-expanded PABPN1. These do not recapitulate OPMD patient genotype and PABPN1 could confound molecular phenotypes. We developed knock-in model (Pabpn1+/A17) that contains one Pabpn1 allele under control native promoter...
The dNab2 polyadenosine RNA binding protein is the D. melanogaster ortholog of vertebrate ZC3H14 protein, which lost in a form inherited intellectual disability (ID). Human can rescue mutant phenotypes when expressed all neurons developing nervous system, suggesting that dNab2/ZC3H14 performs well-conserved roles neurons. However, cellular and molecular requirements for system have not been defined any organism. Here we show autonomously required within to pattern axon projection from Kenyon...
A number of mutations in genes that encode ubiquitously expressed RNA-binding proteins cause tissue specific disease. Many these diseases are neurological nature revealing critical roles for this class the brain. We recently identified a gene encodes polyadenosine protein, ZC3H14 (Zinc finger CysCysCysHis domain-containing protein 14), nonsyndromic, autosomal recessive form intellectual disability. This finding reveals molecular basis disease and provides evidence is essential proper brain...
The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A) RNA binding required for intellectual function. supports memory and axon projection, but its molecular role in neurons undefined. Here, we present network interactions that links to cytoplasmic control neuronal mRNAs conjunction with the fragile X dFMRP. dfmr1 interact genetically neurodevelopment olfactory memory, their encoded proteins co-localize puncta within processes. regulates CaMKII, not futsch, implying selective...
Long-range enhancers of transcription are a key component the genomic regulatory architecture. Recent studies have identified bi-directionally transcribed RNAs emanating from these known as eRNAs. However, it remains unclear how tightly coupled eRNA production is with enhancer activity. Through our systematic search for long-range elements that interact interferon-β gene, model system studying inducible transcription, we novel enhancer, which named L2 regulates expression interferon-β. We...
The Drosophila polyadenosine RNA binding protein Nab2, which is orthologous to a human lost in form of inherited intellectual disability, controls adult locomotion, axon projection, dendritic arborization, and memory through largely undefined set target RNAs. Here, we show specific role for Nab2 regulating splicing ~150 exons/introns the head transcriptome focus on retention male-specific exon sex determination factor Sex-lethal ( Sxl ) that enriched female neurons. Previous studies have...
Background Making the correct choice between transcription elongation and termination is essential to function of RNA polymerase II, fundamental gene expression. This can be influenced by factors modifying complex, chromatin, or signals mediated template transcript. To aid in study we have developed a reporter system that consists tandem luciferase reporters flanking test sequence interest. The ratio expression from provides measure relative rates successful through intervening sequence....
RNA processing is critical for proper spatial and temporal control of gene expression. The ubiquitous nuclear polyadenosine binding protein, PABPN1, post-transcriptionally regulates multiple steps Mutations in the PABPN1 expanding an N-terminal alanine tract protein from 10 alanines to 11-18 cause muscle-specific disease oculopharyngeal muscular dystrophy (OPMD), which affects eyelid, pharynx, proximal limb muscles. Previous work revealed that Pabpn1 transcript unstable, contributing low...
Abstract The Drosophila polyadenosine RNA binding protein Nab2, which is orthologous to a human lost in form of inherited intellectual disability, controls axon projection, locomotion, and memory. Here we define an unexpectedly specific role for Nab2 regulating splicing ∼150 exons/introns the head transcriptome link most prominent these, female retention male-specific exon sex determination factor Sex-lethal ( Sxl ), m 6 A-dependent mRNA splicing. Genetic evidence indicates that aberrant...
Oculopharyngeal muscular dystrophy (OPMD), a late onset disorder affecting specific skeletal muscles, is caused by (GCG)n expansion mutation in the gene encoding mRNA processing protein, polyadenylate binding protein nuclear 1 (PABPN1). The PABPN1 leads to an increase stretch of N-terminal alanine residues from normal 10 12-18. Given this modest change, detection mutant has not been possible without use tagged constructs.We sought generate polyclonal antibody that recognizes alanine-expanded...
Abstract Introduction: Human papilloma virus (HPV) is a causative factor in the genesis of cervical cancer. Curcumin can act as an adjuvant cancer therapy with essentially no side effects. In this study, we elucidated role curcumin to chemo and radiotherapy patients suffering from Experimental Design: This was pilot study Phase III, randomized control, double blind clinical trial. Forty five histopathologically confirmed (stage IIb IIIb) were enrolled. The into Group A/Group B given (4gm/day...
Friedreich ataxia (FRDA) is a neurodegenerative disorder caused by GAA•TTC repeat expansion in the first intron of frataxin gene (FXN). Expanded tracts reduce FXN expression FRDA patients. The mechanisms responsible for remain unclear. development human cellular model instability will provide an experimental system order to better understand leading FRDA. Our employs reporter constructs containing uninterrupted that have been integrated into unique location genome embryonic kidney (HEK) 293...
Friedreich ataxia (FRDA), is a neurodegenerative disease accompanied by hypertrophic cardiomyopathy. FRDA patients suffer an unrelenting progressive and most eventually succumb to cardiac failure. Most are homozygous for large GAA•TTC repeat expansions in the intron 1 of FXN gene. Disease severity directly correlates size expansion, which represses gene expression mechanism that still unclear. In order investigate this inhibition expanded repeats, we designed splicing minigene construct...