A5084671504- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- SARS-CoV-2 and COVID-19 Research
- Cancer-related gene regulation
- RNA regulation and disease
- Epigenetics and DNA Methylation
- SARS-CoV-2 detection and testing
- Cancer-related molecular mechanisms research
- Plant Molecular Biology Research
- COVID-19 Clinical Research Studies
- Chromosomal and Genetic Variations
- COVID-19 diagnosis using AI
- Genomics and Phylogenetic Studies
- Neurogenetic and Muscular Disorders Research
- Animal Genetics and Reproduction
- RNA Interference and Gene Delivery
- Photosynthetic Processes and Mechanisms
- Animal Virus Infections Studies
- Phagocytosis and Immune Regulation
- Bioinformatics and Genomic Networks
- Pluripotent Stem Cells Research
- Cerebrovascular and genetic disorders
University of Toronto
2015-2024
Lunenfeld-Tanenbaum Research Institute
2021
Donnelly College
2018-2021
Oncode Institute
2008-2010
The Netherlands Cancer Institute
2008-2010
Aarhus University
2007
Research Institute of Molecular Pathology
2003-2005
Alternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity eukaryotic genomes. Of different classes AS, intron retention (IR) least well understood. In plants unicellular eukaryotes, IR most common form whereas in animals, it thought to represent prevalent form. Using high-coverage poly(A)(+) RNA-seq data, we observe that surprisingly frequent mammals, affecting transcripts from as many three-quarters multiexonic genes. A highly...
Alternative splicing (AS) generates remarkable regulatory and proteomic complexity in metazoans. However, the functions of most AS events are not known, programs regulated remain to be identified. To address these challenges, we describe Vertebrate Splicing Transcription Database (VastDB), largest resource genome-wide, quantitative profiles assembled date. VastDB provides readily accessible information on inclusion levels functional associations detected RNA-seq data from diverse vertebrate...
Abstract Roifman Syndrome is a rare congenital disorder characterized by growth retardation, cognitive delay, spondyloepiphyseal dysplasia and antibody deficiency. Here we utilize whole-genome sequencing of patients to reveal compound heterozygous variants that disrupt highly conserved positions the RNU4ATAC small nuclear RNA gene, minor spliceosome component essential for intron splicing. Targeted confirms allele segregation in six cases from four unrelated families. have been recently...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein is essential for viral replication, making it a promising target antiviral drug and vaccine development. SARS-CoV-2 infected patients exhibit an uncoordinated immune response; however, the underlying mechanistic details of this imbalance remain obscure. Here, starting from functional proteomics workflow, we cataloged protein-protein interactions proteins, including evolutionarily conserved specific...
Specific interactions of the genome with nuclear lamina (NL) are thought to assist chromosome folding inside nucleus and contribute regulation gene expression. High-resolution mapping has recently identified hundreds large, sharply defined lamina-associated domains (LADs) in human genome, suggested that insulator protein CTCF may help demarcate these domains. Here, we report detailed structure LADs Drosophila cells, investigate putative roles five proteins LAD organization. We found is also...
Translational control of gene expression plays a key role during the early phases embryonic development. Here we describe transcriptional regulator mouse stem cells (mESCs), Yin-yang 2 (YY2), that is controlled by translation inhibitors, Eukaryotic initiation factor 4E-binding proteins (4E-BPs). YY2 critical in regulating mESC functions through pluripotency factors, including Octamer-binding protein 4 (Oct4) and Estrogen-related receptor-β (Esrrb). Importantly, overexpression directs...
Article15 April 2019Open Access Source DataTransparent process A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes Magdalena M Maslon MRC Human Genetics Unit, Institute Molecular Medicine, University Edinburgh, UK Search for more papers by this author Ulrich Braunschweig Donnelly Centre, Department Genetics, Toronto, ON, Canada Stuart Aitken Abigail R Mann Fiona Kilanowski Chris J Hunter Benjamin Blencowe Alberto Kornblihtt Instituto de...
Abstract Population scale sweeps of viral pathogens, such as SARS-CoV-2, require high intensity testing for effective management. Here, we describe “Systematic Parallel Analysis RNA coupled to Sequencing Covid-19 screening” (C19-SPAR-Seq), a multiplexed, scalable, readily automated platform SARS-CoV-2 detection that is capable analyzing tens thousands patient samples in single run. To address strict requirements control assay parameters and output demanded by clinical diagnostics, employ...
In eukaryotes, neighboring genes can be packaged together in specific chromatin structures that ensure their coordinated expression. Examples of such multi-gene domains are well-documented, but a global view the organization eukaryotic genomes is lacking. To systematically identify domains, we constructed compendium genome-scale binding maps for broad panel chromatin-associated proteins Drosophila melanogaster. Next, computationally analyzed this evidence using novel statistical segmentation...
Abstract The spatial partitioning of the transcriptome in cell is an important form gene-expression regulation. Here, we address how intron retention influences spatio-temporal dynamics transcripts from two clinically relevant genes: TERT (Telomerase Reverse Transcriptase) pre-mRNA and TUG1 (Taurine-Upregulated Gene 1) lncRNA. Single molecule RNA FISH reveals that nuclear uniformly robustly retain specific introns. Our data suggest splicing retained introns occurs during mitosis. In...