A5004154228- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Nuclear Structure and Function
- Telomeres, Telomerase, and Senescence
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Nutrition and Health in Aging
- PARP inhibition in cancer therapy
- interferon and immune responses
- Viral Infections and Immunology Research
- Cell death mechanisms and regulation
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Cytomegalovirus and herpesvirus research
- Cytokine Signaling Pathways and Interactions
- DNA Repair Mechanisms
- Cancer therapeutics and mechanisms
- Virus-based gene therapy research
- Lung Cancer Research Studies
McGill University
2012-2024
King Abdullah University of Science and Technology
2021-2024
McGill University Health Centre
2011-2024
Hamad bin Khalifa University
2015-2019
The Ohio State University
2014
Angelina College
2010
Laboratoire de Biochimie
2008
Lerøy (Norway)
2007
Stavros Niarchos Foundation
2007
Yale University
2000-2001
AU-rich elements (AREs) present in the 3′ untranslated regions of many protooncogene, cytokine, and lymphokine messages target them for rapid degradation. HuR, a ubiquitously expressed member ELAV (embryonic lethal abnormal vision) family RNA binding proteins, selectively binds AREs stabilizes ARE-containing mRNAs transiently transfected cells. Here, we identify four mammalian proteins that bind HuR known to be essential its ability shuttle between nucleus cytoplasm stabilize mRNA: SETα,...
AU-rich elements (AREs) located in the 3′ untranslated region target mRNAs encoding many protooncoproteins, cytokines, and lymphokines for rapid degradation. HuR, a ubiquitously expressed member of embryonic lethal abnormal vision (ELAV) family RNA-binding proteins, binds ARE sequences selectively stabilizes ARE-containing reporter when overexpressed transiently transfected cells. HuR appears predominantly nucleoplasmic but has been shown to shuttle between nucleus cytoplasm via novel...
Cytoplasmic aggregates known as stress granules (SGs) arise a consequence of cellular and contain stalled translation preinitiation complexes. These foci are thought to serve sites mRNA storage or triage during the cell response. SG formation has been shown require induction eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate potential role other factors in this process demonstrate that interfering with eIF4A activity, an RNA helicase required for ribosome...
The transport of messenger RNAs (mRNAs) from the nucleus to cytoplasm involves adapter proteins that bind mRNA as well receptor interact with nuclear pore complex. We demonstrate utility cell-permeable peptides designed interfere interactions between potential and define pathways accessed by particular mRNAs. show HuR, a protein implicated in stabilization short-lived mRNAs containing AU-rich elements (AREs), serves an for c-fos export through two pathways. One HuR shuttling domain, HNS,...
The inhibition of the ubiquitin-dependent proteasome system (UPS) via specific drugs is one type approach used to combat cancer. Although it has been suggested that UPS prevents rapid decay AU-rich element (ARE)-containing messages, very little known about cellular mechanisms leading this effect. Here we establish a link between activity, formation cytoplasmic stress granules (SGs), and mRNA metabolism. assembly SGs requires phosphorylation translation initiation factor eIF2alpha by...
Mitogen activation of mRNA decay pathways likely involves specific endoribonucleases, such as G3BP, a phosphorylation-dependent endoribonuclease that associates with RasGAP in dividing but not quiescent cells. G3BP exclusively cleaves between cytosine and adenine (CA) after interaction RNA through the carboxyl-terminal RRM-type binding motif. Accordingly, is tightly associated subset poly(A)(+) mRNAs containing its high-affinity sequence, c-myc mouse embryonic fibroblasts. Interestingly,...
A potential p120 GTPase-activating protein (RasGAP) effector, G3BP (RasGAP Src homology 3 [SH3] binding protein), was previously identified based on its ability to bind the SH3 domain of RasGAP. Here we show that colocalizes and physically interacts with RasGAP at plasma membrane serum-stimulated but not quiescent Chinese hamster lung fibroblasts. In cells, hyperphosphorylated serine residues, this modification essential for activity. Indeed, harbors a phosphorylation-dependent RNase...
Research Article6 March 2017Open Access Source DataTransparent process STAT3 promotes IFNγ/TNFα-induced muscle wasting in an NF-κB-dependent and IL-6-independent manner Jennifer F Ma Department of Biochemistry, Rosalind Morris Goodman Cancer Centre, McGill University, Montreal, QC, Canada Search for more papers by this author Brenda J Sanchez Derek T Hall Anne-Marie K Tremblay Sergio Di Marco Imed-Eddine Gallouzi Corresponding Author [email protected] orcid.org/0000-0003-4758-4835 Life...
Muscle wasting (cachexia) is a consequence of chronic diseases, such as cancer, and associated with degradation muscle proteins MyoD. The cytokines tumor necrosis factor alpha gamma interferon induce degeneration by activating the transcription NF-kappaB its target genes. Here, we show that downstream nitric oxide (NO) synthase gene (iNos) suggest NO production stimulates MyoD mRNA loss. In fact, although cytokine treatment iNos(-/-) mice activated NF-kappaB, it did not trigger degeneration,...
The RNA-binding protein HuR affects cell fate by regulating the stability and/or translation of messenger RNAs that encode stress response proteins. In this study, we delineate a novel regulatory mechanism which contributes to stress-induced death. Upon lethal stress, translocates into cytoplasm involving its association with apoptosome activator pp32/PHAP-I. Depleting expression pp32/PHAP-I RNA interference reduces both cytoplasmic accumulation and efficiency caspase activation. cytoplasm,...
A high expression level of the -actin protein is required for important biological mechanisms, such as maintaining cell shape, growth, and motility.Although elevated cellular directly linked to long half-life its mRNA, molecular mechanisms responsible this effect are unknown.Here we show that RNA-binding HuR stabilizes mRNA by associating with a uridine-rich element within 3 untranslated region.Using RNA interference knock down in HeLa cells, demonstrate plays an role stabilization but not...
Poly(ADP-ribose) (pADPr) is heterogenic molecule synthesized from NAD by poly(ADP-ribose) polymerases (PARPs). Multiple cellular functions are affected pADPr through its network of associated proteins ranging genome integrity surveillance, cell cycle progression, DNA repair to apoptosis. Using quantitative proteomics, we established a temporal map pADPr-associated complexes upon genotoxic stress. Results suggested strong pADPr-association multiple involved in stress granule formation,...
Research Article29 May 2018Open Access Source DataTransparent process The AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation-associated cachectic muscle wasting Derek T Hall Department of Biochemistry, McGill University, Montreal, QC, Canada Rosalind and Morris Goodman Cancer Centre, Search for more papers by this author Takla Griss Physiology, Jennifer F Ma Brenda Janice Sanchez Jason Sadek Anne Marie K Tremblay Souad Mubaid Amr Omer...
Abstract Cellular senescence is a known driver of carcinogenesis and age-related diseases, yet required for various physiological processes. However, the mechanisms factors that control negative effects while retaining its benefits are still elusive. Here, we show rasGAP SH3-binding protein 1 (G3BP1) activation senescent-associated secretory phenotype (SASP). During senescence, G3BP1 achieves this effect by promoting association cyclic GMP-AMP synthase (cGAS) with cytosolic chromatin...
The formation of muscle fibers involves the sequential expression many proteins that regulate key steps during myoblast-to-myotube transition. MyoD, myogenin, and cyclin-dependent kinase inhibitor p21cip1 are major players in initiation maintenance differentiated state mouse embryonic cells (C2C12). messenger RNAs encoding these three contain typical AU-rich elements (AREs) their 3′-untranslated regions (3′-UTRs), which known to affect half-life short-lived mRNAs. HuR, an RNA-binding protein...
Cachexia, or muscle-wasting syndrome, is one of the major causes death in patients affected by diseases such as cancer, AIDS and sepsis. However, no effective anti-cachectic treatment currently available. Here we show that a low dose pateamine A, an inhibitor translation initiation, prevents muscle wasting caused cytokines interferon γ tumour necrosis factor α C26-adenocarcinoma tumours. Surprisingly, although high doses A abrogate general translation, selectively inhibit expression...
Article29 March 2018Open Access Source DataTransparent process Stress granules counteract senescence by sequestration of PAI-1 Amr Omer Department Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, QC, Canada Search for more papers this author Devang Patel Xian Jin Lian Jason Sadek Sergio Di Marco Arnim Pause Myriam Gorospe Laboratory Genetics Genomics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD, USA Imed Eddine Gallouzi...