A5088805938- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Pluripotent Stem Cells Research
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- Fuel Cells and Related Materials
- Microtubule and mitosis dynamics
- Animal Genetics and Reproduction
- Advanced biosensing and bioanalysis techniques
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Neurogenetic and Muscular Disorders Research
- RNA Interference and Gene Delivery
National Institutes of Health
2021-2024
Center for Cancer Research
2022-2024
National Cancer Institute
2021-2024
University of Toronto
2014-2022
University of Dundee
2009-2013
MRC Protein Phosphorylation and Ubiquitylation Unit
2013
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...
Regulation of splicing regulators The messenger RNAs most eukaryotic genes are formed by together a series exons and removing the intervening introns. identity order can vary between mRNAs for same gene. alternatively spliced products generate an increased diversity protein products. Gueroussov et al. show that alternative mammalian regulatory factor affects, in turn, wide range target RNAs. This regulation mechanism controls brain-specific program. Science , this issue p. 868
The 7-methylguanosine cap added to the 5' end of mRNA is required for efficient gene expression in eukaryotes. In mammals, methylation guanosine catalyzed by RNMT (RNA guanine-7 methyltransferase), an enzyme previously thought function as a monomer. We have identified obligate component mammalian methyltransferase, RAM (RNMT-Activating Mini protein)/Fam103a1, uncharacterized protein. consists N-terminal RNMT-activating domain and C-terminal RNA-binding domain. As monomers relatively weak...
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...
CRISPR-Cas technology has transformed functional genomics, yet understanding of how individual exons differentially shape cellular phenotypes remains limited. Here, we optimized and conducted massively parallel exon deletion splice-site mutation screens in human cell lines to identify that regulate fitness. Fitness-promoting are prevalent essential highly expressed genes commonly overlap with protein domains interaction interfaces. Conversely, fitness-suppressing enriched nonessential genes,...
The c-Myc proto-oncogene promotes mRNA cap methylation, which is essential for almost all translation. methylation reaction produces an inhibitory byproduct, S-adenosyl homocysteine. Here we report that Myc upregulation of homocysteine hydrolase (SAHH), enzyme hydrolyzes homocysteine, thus neutralizing its effects, and this required c-Myc-induced methylation. was repressed by inhibiting the expression or activity SAHH, whereas same treatments did not have a significant effect on...
Eukaryotic gene expression is dependent on the modification of first transcribed nucleotide pre-mRNA by addition 7-methylguanosine cap. The cap protects transcripts from exonucleases and recruits complexes which mediate transcription elongation, processing translation initiation. synthesized a series reactions link to via 5' triphosphate bridge. In mammals, synthesis catalysed sequential action RNGTT (RNA guanylyltransferase 5'-phosphatase) RNMT guanine-7 methyltransferase), enzymes...
Abstract Intron retention (IR) is a form of alternative splicing in which an intron that should be spliced out from precursor transcript, retained the mature RNA after completed. Although there emerging evidence widespread IR protein-coding genes and long noncoding RNAs (lncRNAs), underlying molecular mechanisms remain largely unclear. Here, we report discovery novel transcripts p53-induced lncRNA PURPL, 2 retained. To determine mechanism(s) conducted CRISPR-based screen 3 different cell...