A5055384658- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- Statistical and Computational Modeling
- Neural Networks and Applications
- Neurogenetic and Muscular Disorders Research
- Gene expression and cancer classification
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Protein Degradation and Inhibitors
- Molecular Biology Techniques and Applications
- Genetic and phenotypic traits in livestock
- Mitochondrial Function and Pathology
- Tumors and Oncological Cases
- Yeasts and Rust Fungi Studies
- Genetic and rare skin diseases.
- Horticultural and Viticultural Research
- Plant Pathogens and Fungal Diseases
- Autism Spectrum Disorder Research
- Fungal and yeast genetics research
- Cancer and Skin Lesions
Stanford University
2019-2022
University of Michigan
2015-2022
University of California, San Diego
2011
Abstract A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is depletion RNA-binding protein TDP-43 from nucleus neurons in brain spinal cord 1 . major function as a repressor cryptic exon inclusion during RNA splicing 2–4 Single nucleotide polymorphisms UNC13A are among strongest hits associated with FTD ALS human genome-wide association studies 5,6 , but how those variants increase risk for disease...
Abstract CGG repeat expansions in the FMR1 5’UTR cause neurodegenerative disease Fragile X-associated tremor/ataxia syndrome (FXTAS). These repeats form stable RNA secondary structures that support aberrant translation absence of an AUG start codon (RAN translation), producing aggregate-prone peptides accumulate within intranuclear neuronal inclusions and contribute to neurotoxicity. Here, we show most abundant RAN product, FMRpolyG, is markedly less toxic when generated from a construct...
Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability and autism. It results from expansion a CGG nucleotide repeat in 5' untranslated region (UTR) FMR1. Large expansions elicit promoter hyper-methylation, heterochromatin formation, FMR1 transcriptional silencing loss protein, FMRP. Efforts aimed at correcting sequelae resultant FMRP have thus far proven insufficient, perhaps because FMRP's pleiotropic functions. As repeats do not disrupt coding sequence,...
Active protein translation can be assessed and measured using ribosome profiling sequencing strategies. Prevailing analytical approaches applied to this technology make use of sequence fragment length or reading frame occupancy enrichment differentiate between active background noise, however they do not consider additional characteristics inherent the which limits their overall accuracy.Here, we present an tool that models tri-nucleotide periodicity ribosomal a classifier based on spectral...
Upstream open reading frames (uORFs) initiate translation within mRNA 5′ leaders, and have the potential to alter main coding sequence (CDS) on transcripts in which they reside. Ribosome profiling (RP) studies suggest that translating ribosomes are pervasive leaders across model systems. However, significance of this observation remains unclear. To explore a role for uORF usage neuronal differentiation, we performed RP undifferentiated differentiated human neuroblastoma cells. Using spectral...
Alternative pre-mRNA splicing allows dramatic expansion of the eukaryotic proteome and facilitates cellular response to changes in environmental conditions.The Saccharomyces cerevisiae gene SUS1, which encodes a protein involved mRNA export histone H2B deubiquitination, contains two introns; non-canonical sequences first intron contribute its retention, common form alternative plants fungi.Here we show that pattern SUS1 change such as temperature elevation, retained product is subject...
Mutations in the ataxin-2 gene (ATXN2) cause neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2). A therapeutic strategy using antisense oligonucleotides targeting ATXN2 has entered clinical trial humans. Additional ways to decrease levels could lead cheaper or less invasive therapies elucidate how is normally regulated. Here, we perform a genome-wide fluorescence-activated cell sorting (FACS)-based CRISPR-Cas9 screen human cells identify...
A hallmark pathological feature of neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion RNA-binding protein TDP-43 from nucleus neurons in brain spinal cord. major function as a repressor cryptic exon inclusion during RNA splicing. Single nucleotide polymorphisms (SNPs) UNC13A are among strongest genome-wide association study (GWAS) hits associated with FTD/ALS humans, but how those variants increase risk for disease unknown. Here...
Gene-based therapeutic strategies to lower ataxin-2 levels are emerging for the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2). Additional of could be beneficial. Here, we perform a genome-wide arrayed small interfering RNA (siRNA) screen in human cells identify RTN4R, gene encoding RTN4/NoGo-Receptor, as potent modifier levels. RTN4R knockdown, or treatment with peptide inhibitor, is sufficient protein mouse neurons vitro, Rtn4r...
ABSTRACT Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability and autism. It results from expansion a CGG nucleotide repeat in 5’ untranslated region FMR1. Large expansions elicit promoter hyper-methylation, heterochromatin formation, FMR1 transcriptional silencing, loss protein, FMRP. Efforts aimed at correcting sequelae resultant FMRP have thus far proven insufficient, perhaps because FMRP’s pleiotropic functions. As repeats do not disrupt coding sequence,...
Abstract Upstream open reading frames (uORFs) initiate translation within mRNA 5’ leaders, and have the potential to alter main coding sequence (CDS) on transcripts in which they reside. Ribosome profiling (RP) studies suggest that translating ribosomes are pervasive leaders across model systems. However, significance of this observation remains unclear. To explore a role for uORF usage neuronal differentiation, we performed RP undifferentiated differentiated human neuroblastoma cells. Using...
Abstract Summary: Active protein translation can be assessed and measured using ribosome profiling sequencing strategies. Existing analytical approaches applied to this technology make use of sequence fragment length or frame occupancy differentiate between active background noise, however they do not consider additional characteristics inherent the which limits their overall accuracy. Here, we present an tool that models tri-nucleotide periodicity ribosomal a classifier based on spectral...