A5026668972- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- PI3K/AKT/mTOR signaling in cancer
- Venomous Animal Envenomation and Studies
- Healthcare and Venom Research
- Polyamine Metabolism and Applications
- Cancer-related gene regulation
- DNA and Nucleic Acid Chemistry
- Marine Invertebrate Physiology and Ecology
- RNA Interference and Gene Delivery
Université de Montréal
2021-2024
Institute for Research in Immunology and Cancer
2021-2024
Université Laval
2015-2022
Polytechnique Montréal
2021
Transcription of the several hundred mouse and human Ribosomal RNA (rRNA) genes accounts for majority synthesis in cell nucleus is determinant cytoplasmic ribosome abundance, a key factor regulating gene expression. The rRNA genes, referred to globally as rDNA, are clustered direct repeats at Nucleolar Organiser Regions, NORs, chromosomes, many cells active transcribed near saturation levels. rDNA also hotspot recombination chromosome breakage, hence understanding its control has broad...
Abstract In the search for drugs to effectively treat cancer, last 10 years have seen a resurgence of interest in targeting ribosome biogenesis. CX-5461 is potential inhibitor ribosomal RNA synthesis that now showing promise phase I trials as chemotherapeutic agent range malignancies. Here, we show irreversibly inhibits transcription by arresting polymerase (RPI/Pol1/PolR1) initiation complex. does not achieve this preventing formation pre-initiation complex nor it affect promoter...
The eukaryotic translation initiation factor eIF4E acts as a multifunctional that simultaneously influences mRNA processing, export, and in many organisms. Its multifactorial effects are derived from its capacity to bind the methyl-7-guanosine cap on 5'end of mRNAs thus can act chaperone for transcripts nucleus cytoplasm. In this review, we describe roles major mRNA-processing events including capping, splicing, cleavage polyadenylation, nuclear export translation. We discuss evidence at two...
Abstract Aberrant splicing is typically attributed to splice‐factor (SF) mutation and contributes malignancies including acute myeloid leukemia (AML). Here, we discovered a mutation‐independent means extensively reprogram alternative (AS). We showed that the dysregulated expression of eukaryotic translation initiation factor eIF4E elevated selective production, thereby impacting multiple spliceosome complexes, factors mutated in AML such as SF3B1 U2AF1. These changes generated landscape...
The combination of Chromatin Immunoprecipitation and Massively Parallel Sequencing, or ChIP-Seq, has greatly advanced our genome-wide understanding chromatin enhancer structures. However, its resolution at any given genetic locus is limited by several factors. In applying ChIP-Seq to the study ribosomal RNA genes, we found that a major limitation was imposed underlying variability in sequence coverage very often dominates protein-DNA interaction profiles. Here, describe simple numerical...
// Nourdine Hamdane 1, 2, 3 , Chelsea Herdman 2 Jean-Clement Mars Victor Stefanovsky 1 Michel G. Tremblay Tom Moss Laboratory of Growth and Development, St-Patrick Research Group in Basic Oncology, Cancer Division the Quebec University Hospital Centre, Québec, QC, Canada Department Molecular Biology, Medical Biochemistry Pathology, Faculty Medicine, Laval University, Present address: Inserm, U1110, Institute Viral Liver Diseases, Strasbourg, France Correspondence to: Moss, e-mail:...
Transcription of the ~200 mouse and human ribosomal RNA genes (rDNA) by Polymerase I (RPI/PolR1) accounts for 80% total cellular RNA, around 35% all nuclear synthesis, determines cytoplasmic ribosome complement. It is therefore a major factor controlling cell growth its misfunction has been implicated in hypertrophic developmental disorders. Activation each rDNA repeat requires nucleosome replacement architectural multi-HMGbox UBTF to create 15.7 kbp free region (NFR). Formation this NFR...
Transcription of the ribosomal RNA precursor by polymerase (Pol) I is a major determinant cellular growth, and dysregulation observed in many cancer types. Here, we present purification human Pol from cells carrying genomic GFP fusion on largest subunit allowing structural functional analysis enzyme across species. In contrast to yeast, carries single-subunit stalk, vitro transcription indicates reduced proofreading activity. Determination cryo-EM reconstruction close-to-native state...
Abstract Aberrant RNA splicing contributes to the pathogenesis of many malignancies including Acute Myeloid Leukemia (AML). While mutation is best described mechanism underpinning aberrant splicing, recent studies show that predictions based on mutations alone likely underestimate extent this dysregulation. Here, we elevation eukaryotic translation initiation factor eIF4E reprogrammes nearly a thousand RNAs in model cell lines. Further, AML patient specimens which did not harbour known...
ABSTRACT Transcription of the ∼200 mouse and human ribosomal RNA genes (rDNA) by Polymerase I (RPI/PolR1) accounts for 80% total cellular RNA, around 35% all nuclear synthesis, determines cytoplasmic ribosome complement. It is therefore a major factor controlling cell growth its misfunction has been implicated in hypertrophic developmental disorders. Activation each rDNA repeat requires nucleosome replacement architectural multi-HMGbox UBTF to create 15kbp free region (NFR). Formation this...
Abstract Transcription of the ribosomal RNA precursor by polymerase (Pol) I is a major determinant cellular growth and dysregulation observed in many cancer types. Here, we present purification human Pol from cells carrying genomic GFP-fusion on largest subunit allowing structural functional analysis enzyme across species. In contrast to yeast, carries single-subunit stalk vitro transcription indicates reduced proofreading activity. Determination cryo-EM reconstruction close-to-native state...