A5006027019- RNA Research and Splicing
- MicroRNA in disease regulation
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Circular RNAs in diseases
- Physiological and biochemical adaptations
- Invertebrate Immune Response Mechanisms
- RNA and protein synthesis mechanisms
- Neurobiology and Insect Physiology Research
- Plant Molecular Biology Research
- Global Health Care Issues
- Mosquito-borne diseases and control
- Mitochondrial Function and Pathology
- Advanced biosensing and bioanalysis techniques
- Health and Well-being Studies
- Aging and Gerontology Research
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Insect symbiosis and bacterial influences
- Endoplasmic Reticulum Stress and Disease
- Viral Infections and Vectors
- RNA regulation and disease
- Cellular transport and secretion
Shiv Nadar University
2023-2024
Regional Centre for Biotechnology
2019-2022
Indiana University Bloomington
2011-2020
Indiana University
2012-2020
Howard Hughes Medical Institute
2007-2012
University of California, Los Angeles
2007-2012
Gauhati Medical College and Hospital
2012
Indian Institute of Science Bangalore
2000-2003
Many metazoan gene transcripts exhibit neuron-specific splicing patterns, but the developmental control of these events is poorly understood. We show that a large group exons reprogrammed during neuronal development by switch in expression between two highly similar polypyrimidine tract-binding proteins, PTB and nPTB (neural PTB). well-studied regulator alternative splicing, closely related paralog whose functional relationship to unknown. In brain, protein specifically expressed...
Alternative pre-mRNA splicing determines many changes in gene expression during development. Two regulators known to control patterns neuron and muscle differentiation are the polypyrimidine tract-binding protein (PTB) its neuronal homolog nPTB. These proteins repress certain exons early myoblasts, but upon of mature myotubes PTB/nPTB is reduced, leading increased inclusion their target exons. We show here that repression nPTB myoblast results from targeting by muscle-restricted microRNA...
Macrophage-mediated phagocytosis and cytokine production represent the front lines of resistance to bacterial invaders. A key feature this pro-inflammatory response in mammals is complex remodeling cellular metabolism towards aerobic glycolysis. Although function bactericidal macrophages highly conserved, metabolic insect remains poorly understood. Here, we used adults fruit fly Drosophila melanogaster investigate changes that occur during acute resolution phases Streptococcus-induced...
AbstractSam68 (Src-associated in mitosis, 68 kDa) is a KH domain RNA binding protein implicated variety of cellular processes, including alternative pre-mRNA splicing, but its functions are not well understood. Using interference knockdown Sam68 expression and splicing-sensitive microarrays, we identified set exons whose splicing depends on Sam68. Detailed analysis one newly target exon epsilon sarcoglycan (Sgce) showed that both elements distributed across the adjacent introns activity...
Steroid hormones and their nuclear receptors drive developmental transitions in diverse organisms, including mammals. In this study, we show that the Drosophila steroid hormone 20-hydroxyecdysone (20E) its receptor directly activate transcription of evolutionarily conserved let-7-complex (let-7-C) locus, which encodes co-transcribed microRNAs miR-100, let-7 miR-125. These small RNAs post-transcriptionally regulate expression target genes, are required for remodeling neuromusculature during...
Significance Oncometabolites are small molecules that promote tumor formation and growth. L-2-hydroxyglutarate (L-2HG) is a putative oncometabolite associated with gliomas renal cell carcinomas, as well severe neurometabolic disorder known L-2-hydroxyglutaric aciduria. However, despite L-2HG commonly considered metabolic waste product, this compound was recently discovered to control immune fate, thereby demonstrating it has endogenous functions in healthy animal cells. Here, we find the...
Messenger RNAs (mRNAs) often contain binding sites for multiple, different microRNAs (miRNAs). However, the biological significance of this feature is unclear, since such co-targeting miRNAs could function coordinately, independently, or redundantly with one another. Here, we show that two co-transcribed Drosophila miRNAs, let-7 and miR-125, non-redundantly regulate a common target, transcription factor Chronologically Inappropriate Morphogenesis (Chinmo). We first characterize novel adult...
CaV1.2 calcium channels play roles in diverse cellular processes such as gene regulation, muscle contraction, and membrane excitation are diversified their activity through extensive alternative splicing of the mRNA. The mutually exclusive exons 8a 8 encode alternate forms transmembrane segment 6 (IS6) channel domain 1. human genetic disorder Timothy syndrome is caused by mutations either these two exons, resulting disrupted Ca(2+) homeostasis severe pleiotropic disease phenotypes....
Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, fly homolog of OXR1, which influenced lifespan and mtd expression response to DR. Knockdown adulthood inhibited DR-mediated extension female flies. found that mtd/OXR1 declines with age it interacts retromer, regulates trafficking proteins lipids. Loss destabilized causing improper protein endolysosomal defects. Overexpression retromer genes or pharmacological restabilization R55...
Adenosine deaminases acting on RNAs (ADARs) convert adenosine residues to inosines in primary microRNA (pri-miRNA) transcripts alter the structural conformation of these precursors and subsequent functions encoded microRNAs (miRNAs). Here we show that RNA editing by Drosophila ADAR modulates expression three co-transcribed miRNAs evolutionarily conserved let-7-Complex (let-7-C) locus. For example, a single A-to-I change at −6 residue pri-miR-100, first miRNA this let-7-C polycistronic...
The dramatic growth that occurs during Drosophila larval development requires rapid conversion of nutrients into biomass. Many tissues respond to these biosynthetic demands by increasing carbohydrate metabolism and lactate dehydrogenase (dLDH) activity. resulting metabolic program is ideally suited synthesize macromolecules mimics the manner which cancer cells rely on aerobic glycolysis. To explore potential role dLDH in promoting biosynthesis, we examined how dLdh mutations influence...
Cell growth and/or proliferation may require the reprogramming of metabolic pathways, whereby a switch from oxidative to glycolytic metabolism diverts intermediates towards anabolic pathways. Herein, we identify novel role for TRIM32 in maintenance flux mediated by biochemical interactions with enzymes Aldolase and Phosphoglycerate mutase. Loss Drosophila TRIM32, encoded thin (tn), shows reduced levels amino acids. This altered profile correlates reduction size larval muscle brain tissue....
Significance Understanding the neuronal functions of diverse RNA pathways will lead to treatments human neurological diseases that are caused by perturbations in metabolism. Two proteins, Drosha and Pasha/DGCR8, play important roles neurons, where they responsible for biogenesis many microRNAs. Here, we show Pasha/DGCR8 also promotes morphogenesis neurons developing fruit flies independently therefore most microRNA production. These studies illuminate a novel function Pasha is medically...
Drosophila melanogaster larval development relies on a specialized metabolic state that utilizes carbohydrates and other dietary nutrients to promote rapid growth. One unique feature of the program is Lactate Dehydrogenase (Ldh) activity highly elevated during this growth phase when compared stages fly life cycle, indicating Ldh serves key role in promoting juvenile development. Previous studies have largely focused function enzyme at whole animal level, however, expression varies...
Dietary restriction (DR) extends healthy lifespan in diverse species. Age and nutrient-related changes the abundance of microRNAs (miRNAs) their processing factors have been linked to organismal longevity. However, mechanisms by which they modulate tissue-specific role miRNA-mediated networks DR-dependent enhancement remains largely unexplored. We show that two neuronally enriched highly conserved microRNAs, miR-125 let-7 mediate DR response Drosophila melanogaster . Functional...
Saccharomyces cerevisiaePRP17 (CDC40) encodes a second‐step pre‐mRNA splicing factor with role in cell division. The functions of Prp17 specific cycle transitions were examined using temperature‐sensitive alleles arrest/release experiments. We find that G1/S and G2/M depend on Prp17. G1‐synchronized prp17::LEU2 cells arrest at non‐permissive temperatures as unbudded haploid low levels CLN1, CLB5 RNR1 transcripts. This indicates execution point or prior to Start. Reduced α‐tubulin protein,...
Evaluation of nutritionally enhanced biofortified dietary interventions that increase lifespan may uncover cost-effective and sustainable approaches for treatment age-related morbidities increasing healthy life expectancy. In this study, we report anthocyanin rich, high yielding crossbred blue wheat prolongs Drosophila melanogaster in different contexts. addition to functioning as an antioxidant rich intervention, the also works through modulating expression DR pathway genes including AMPK...
During Drosophila melanogaster metamorphosis, arrested immature neurons born during larval development differentiate into their functional adult form. This differentiation coincides with the downregulation of two zinc-finger transcription factors, Chronologically Inappropriate Morphogenesis (Chinmo) and Z3 isoform Broad (Br-Z3). Here, we show that br-Z3 is regulated by microRNAs, let-7 miR-125, are activated at larval-to-pupal transition known to also regulate chinmo The 3'UTR contains...
In Saccharomyces cerevisiae, Prp17p is required for the efficient completion of second step pre-mRNA splicing. The function and interacting factors this protein have not been elucidated. We performed a mutational analysis yPrp17p to identify domains critical function. A series deletions were made throughout region spanning N-terminal 158 amino acids protein, which do contain any identified structural motifs. C-terminal portion (amino 160–455) contains WD domain containing seven repeats....