A5066531693- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Infectious Diseases and Mycology
- Retinal Development and Disorders
- interferon and immune responses
- Single-cell and spatial transcriptomics
- Parasite Biology and Host Interactions
- Plant Pathogens and Fungal Diseases
- Plant Pathogens and Resistance
- Muscle Physiology and Disorders
- Parasitic Diseases Research and Treatment
- RNA regulation and disease
- MicroRNA in disease regulation
- Leprosy Research and Treatment
- Parasites and Host Interactions
- Genomics and Chromatin Dynamics
- Neurogenesis and neuroplasticity mechanisms
- Protist diversity and phylogeny
- Identification and Quantification in Food
- Genetic Neurodegenerative Diseases
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Genital Health and Disease
- Mediterranean and Iberian flora and fauna
University of Connecticut
2015-2024
Institute for Systems Biology
2018-2022
Howard Hughes Medical Institute
2008-2011
Harvard University
2008-2011
University of Florida
2003-2006
Florida College
2003-2006
University of Rochester
2003
Bethune-Cookman University
1997-1999
The neuromuscular disease myotonic dystrophy (DM) is caused by microsatellite repeat expansions at two different genomic loci. Mutant DM transcripts are retained in the nucleus together with muscleblind (Mbnl) proteins, and these abnormal RNAs somehow interfere pre-mRNA splicing regulation. Here, we show that disruption of mouse Mbnl1 gene leads to muscle, eye, RNA abnormalities characteristic disease. Our results support hypothesis manifestations can result from sequestration specific...
In myotonic dystrophy (DM), expression of RNA containing expanded CUG or CCUG repeats leads to misregulated alternative splicing pre-mRNA. The repeat-bearing transcripts accumulate in nuclear foci, together with proteins the muscleblind family, MBNL1 and MBNL2. transgenic mice that express repeats, we show defect selectively targets a group exons share common temporal pattern developmental regulation. These undergo synchronized switch between post-natal day 2 20 wild-type mice. During this...
RNA-mediated pathogenesis is a recently developed disease model that proposes certain types of mutant genes produce toxic transcripts inhibit the activities specific proteins. This was proposed first for neuromuscular myotonic dystrophy (DM), which associated with expansion structurally related (CTG)(n) and (CCTG)(n) microsatellites in two unrelated genes. At RNA level, these expansions form stable hairpins alter pre-mRNA splicing antagonistic factor families, MBNL CELF It unclear altered...
Mutations in minor spliceosome components such as U12 snRNA (cerebellar ataxia) and U4atac (microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1)) result tissue-specific symptoms. Given that the is ubiquitously expressed, we hypothesized these restricted phenotypes might be caused by regulation of targets, i.e. intron-containing genes (MIGs). The current model inefficient splicing thought to apply ~ 500 MIGs identified U12DB. However this database was created more than 10 years...
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly. While histopathology different disease stages well characterized, underlying progression, from early drusen stage to advanced that leads blindness, remains unknown. Here, we show photoreceptors (PRs) diseased individuals display increased expression two key glycolytic genes, suggestive a glucose shortage during disease. Mimicking aspects this metabolic profile PRs wild-type mice by activation mammalian...
Local translation can support memory consolidation by supplying new proteins to synapses undergoing plasticity. Translation in adult forebrain dendrites is an established mechanism of synaptic plasticity and regulated learning, yet there no evidence for learning-regulated protein synthesis axons, which have traditionally been believed be incapable translation. Here, we show that axons the rat amygdala contain machinery, use translating ribosome affinity purification (TRAP) with RNASeq...
ABSTRACT Mutation in minor spliceosome components is linked to the developmental disorder microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Here, we inactivated developing mouse cortex (pallium) by ablating Rnu11, which encodes crucial small nuclear RNA (snRNA) U11. Rnu11 conditional knockout mice were born with microcephaly, was caused death of self-amplifying radial glial cells (RGCs), while intermediate progenitor and neurons produced. sequencing suggested that this cell...
Vertebrate genomes contain major (>99.5%) and minor (<0.5%) introns that are spliced by the spliceosomes, respectively. Major intron splicing follows exon-definition model, whereby spliceosome components first assemble across exons. However, since most genes with predominately consist of introns, formation complexes in these would require interaction between spliceosomes. Here, we report protein U11-59K binds to U2AF complex, thereby supporting a model which interacts an exon regulate...
The evolutionarily conserved minor spliceosome (MiS) is required for protein expression of ∼714 intron-containing genes (MIGs) crucial cell-cycle regulation, DNA repair, and MAP-kinase signaling. We explored the role MIGs MiS in cancer, taking prostate cancer (PCa) as an exemplar. Both androgen receptor signaling elevated levels U6atac, a small nuclear RNA, regulate activity, which highest advanced metastatic PCa. siU6atac-mediated inhibition PCa vitro model systems resulted aberrant intron...
Minor introns constitute <0.5% of the in human genome and have remained an enigma since their discovery. These are removed by a distinct splicing complex, minor spliceosome. Both ancient, tracing back to last eukaryotic common ancestor (LECA), which is reflected intron enrichment specific gene families, such as MAP kinases, voltage-gated sodium calcium ion channels, E2F transcription factors. Most occur single genes with predominantly major introns. Due this organization, intron-containing...
In eukaryotes, gene expression requires splicing, which starts with the identification of exon-intron boundaries by small, nuclear RNA (snRNAs) spliceosome, aided associated proteins. mammalian genome, <1% introns lack canonical boundary sequences and cannot be spliced splicing machinery. These are minor consisting unique snRNAs (U11, U12, U4atac, U6atac). The importance spliceosome is underscored disease microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1), caused mutation in...
Abstract After removing nonspecific immunoreactivities from crude extract by immunoaffinity chromatography, an immunoreactive‐band at 60kDa of constitutive nitric oxide synthase (cNOS) Saccharomyces cerevisiae was detected Western blot using mouse monoclonal anti‐neuronal NOS (cNOS). The activity yeast cNOS, which prepared either histone‐agarose chromatography or immunoprecipitation, monitored the formation citrulline. Yeast cNOS activated in presence calmodulin and arginine, whereas it...
In the mammalian genome, each histone family contains multiple replication-dependent paralogs, which are found in clusters where their transcription is thought to be coupled cell cycle. Here, we wanted interrogate transcriptional regulation of these paralogs during retinal development and aging. We employed deep sequencing, quantitative PCR, situ hybridization (ISH), microarray analysis, revealed that genes were not only transcribed progenitor cells but also differentiating neurons....
Massively parallel whole transcriptome sequencing, commonly referred to as RNA-Seq, has become the technology of choice for performing gene expression profiling. However, reconstruction full-length novel transcripts from RNA-Seq data remains challenging due short read length delivered by most existing sequencing technologies. We propose a statistical genome-guided method called "Transcriptome Reconstruction using Integer Programming" (TRIP) that incorporates fragment distribution into...