Pascal Chartrand
Molecular imaging and cellular dynamics of RNA
- Professeur titulaire
-
Faculté de médecine - Département de biochimie et médecine moléculaire
Roger-Gaudry, room D507
Media
Cérémonie Bravo à nos chercheurs - 6 mai 2015
© Université de Montréal
Profile
Research expertise
1) Intracellular trafficking of telomerase RNA and its role in biogenesis and regulation of its activity
Telomeres protect the ends of chromosomes in eukaryotic cells by preventing their degradation and fusion. In most eukaryotes, telomerase reverse transcriptase is responsible for telomere elongation. This enzyme consists of an RNA subunit containing the template, to which protein subunits responsible for catalytic activity bind. Telomerase plays a crucial role in cell transformation since it is reactivated in the majority of cancers and allows the immortalization of cancer cells. Our laboratory particularly uses single-molecule imaging to explore: 1) the intracellular trafficking of telomerase RNA and its role in the biogenesis of this holoenzyme, as well as 2) the role of non-coding telomeric RNAs in the regulation of telomerase activity.
2) Pathogenesis of Myotonic Dystrophy type 1 (DM1)
DM1 is a rare and incurable neuromuscular genetic disease which affects 1 in 8,000 people. Over time, patients develop lung and heart complications that render them disabled and limit their life expectancy. This disease is caused by the accumulation of CTG triplet repeats in the DMPK gene, which leads to the aggregation of its mRNA as nuclear foci in muscle cells. The current hypothesis of a toxic effect of this mRNA posits that the nuclear retention of the mutant DMPK mRNA alters the function of regulatory RNA-binding proteins, which as sequestered on the mutant transcript. Our laboratory studies 1) the role of non-coding RNAs in the pathogenesis of DM1, 2) aims to identify proteins associated with RNAs containing expanded triplet repeats, and 3) develop pharmacological treatments for this disease.
3) Mechanisms of intracellular transport of mRNAs and their local translation
mRNA localization is used by different types of polarized cells to locally translate specific proteins and thus restrict their distribution to a particular region of the cytoplasm. This mechanism offers the possibility of locally and temporally regulate the expression of proteins. The transport and localization of specific mRNAs plays an important role during the development of multicellular organisms, as well as in biological processes such as synaptic transmission, cell motility and asymmetric cell division. Our laboratory uses the localization of mRNA in the bud of the yeast Saccharomyces cerevisiae as a model organism. We seek to: 1) understand the mechanisms of recognition of localized mRNAs and assembly of the localization machinery on these mRNAs, and 2) identify and characterize the factors responsible for controlling the translation of mRNAs during their transport.
Awards and recognitions
- Chaire de Recherche FRQS (2015-2019)
- Chercheur-boursier Senior FRSQ (2009-2013)
- Chercheur-boursier Junior 2 FRSQ (2006-2009)
- Chercheur-boursier Junior 1 FCAR (2001-2006)
Affiliations and responsabilities
Research affiliations
Teaching and supervision
Teaching
Student supervision
Theses and dissertation supervision (Papyrus Institutional Repository)
Phosphorylation of the RNA-binding protein She2 and its impact on mRNA localization in yeast
Cycle : Doctoral
Grade : Ph. D.
Étude de la régulation de la télomérase par imagerie en molécules uniques
Cycle : Master's
Grade : M. Sc.
Imagerie moléculaire de l’ARN de la télomérase dans des cellules cancéreuses humaines
Cycle : Doctoral
Grade : Ph. D.
Régulation de l’expression et de la localisation des ARN TLC1 et TERRA en réponse à différents stress génomiques chez la levure
Cycle : Doctoral
Grade : Ph. D.
Étude de l’expression et des partenaires protéiques de l’ARN TERRA (TElomeric Repeat-containing RNA) dans les cellules de cancer humaines
Cycle : Master's
Grade : M. Sc.
Localisation de l'ARNm STAT3 aux protrusions des cellules du carcinome hépatocellulaire associées à un phénotype métastatique
Cycle : Master's
Grade : M. Sc.
Étude du rôle des ARN non codants du cluster Dlk1-Dio3 dans la dystrophie myotonique de type 1
Cycle : Master's
Grade : M. Sc.
Trafic intranucléaire de l’ARN de la télomérase et la réponse aux dommages à l’ADN chez la levure Saccharomyces cerevisiae
Cycle : Doctoral
Grade : Ph. D.
La voie de régulation de la traduction de l’ARNm ASH1 : une concertation entre Khd1, Puf6 et Loc1
Cycle : Master's
Grade : M. Sc.
Exploring TERRA (TElomeric Repeat-containing RNA) Expression and Regulation During Cell Growth in Saccharomyces cerevisiae
Cycle : Master's
Grade : M. Sc.
A mechanism for co-transcriptional recruitment of mRNA localization factor on nascent mRNAs in budding yeast
Cycle : Doctoral
Grade : Ph. D.
The role of GAPDH in maintaining the functional state of the DNA repair enzyme APE1
Cycle : Master's
Grade : M. Sc.
Trafic intracellulaire de l’ARN de la télomérase chez Saccharomyces cerevisiæ : relation entre biogénèse de la télomérase et homéostasie des télomères
Cycle : Doctoral
Grade : Ph. D.
Le vieillissement chronologique de Schizosaccharomyces pombe : Implication des voies de détection du glucose
Cycle : Doctoral
Grade : Ph. D.
Études des modifications post-traductionnelles de Khd1p et de leur rôle dans la régulation de la traduction de l'ARNm ASH1 chez la levure Saccharomyces cerrevisiae
Cycle : Doctoral
Grade : Ph. D.
Étude du mécanisme d'autorégulation entre les facteurs de transcription E2F et le microARN miR-20a
Cycle : Master's
Grade : M. Sc.
Étude des éléments impliqués dans le transport et la régulation traductionnelle de l'ARNm ASH1 chez la levure Saccharomyces cerevisiae
Cycle : Master's
Grade : M. Sc.
Dynamique de la traduction de l'ARNm ASHI chez la levure Saccharomyces cerevisiae
Cycle : Master's
Grade : M. Sc.
Projects
Research projects
Defining the repertoires and functional impacts of RNA binding proteins that undergo sequestration by toxic repeat RNA
Defining the repertoires and functional impacts of RNA binding proteins that undergo sequestration by toxic repeat RNA
Studying telomeres maintenance by telomerase using live cell imaging
Mechanisms regulating mRNA localization and localized translation
Investigating telomerase dynamics in live cells at a single-molecule level
Pre-clinical testing of novel pharmacological inhibitors of toxic DMPK mRNA in a DM1 mouse model
Pre-clinical testing of novel pharmacological inhibitors of toxic DMPK mRNA in a DM1 mouse model
Exploring the impact of mutation in the budding yeast DNAJC21-homolog JJJ1 on telomerase biogenesis
Supplément COVID-19 CRSNG_Mechanisms regulating mRNA localization and localized translation
4th Canadian Symposium on Telomeres and Genomics Integrity
MECHANISMS REGULATING MRNA LOCALIZATION AND TRANSLATIONAL CONTROL
ROLE BIOLOGIQUES ET IMPLICATIONS PATHOLOGIQUE DE LA DYNAMIQUE ET DE LA LOCALISATOIN INTRACELLULAIRE DE COMPLEE RIBONUCLEOPROTEIQUE
"Rare diseases: models & mechanisms" network (RDMM) / réseau Canadien "maladies rares: modèles et mécanismes" (MRMM) Exploring the impact of mutation in the budding yeast DNAJC21-homolog JJJ1 on ribosome and telomerase biogenesis
SINGLE CELL ANALYSIS OF TELOMERASE ACTIVITY AND REGULATION
THE ROLES OF MBNL PROTEINS IN THE PATHOGENESIS OF MYOTONIC DYSTROPHY
INHIBITORY COMPOUNDS OF POLYNYCLEOTIDE REPEAT-ASSOCIATED RNA-FOCI - ÉTUDE PRÉCLINIQUE DE COMPOSÉS PHARMACOLOGIQUES POUR LA TRAITEMENT DE LA DYSTROPHIE MUSCULAIRE
PATHOGENESIS OF MYOTONIC DYSTROPHY
INHIBITORY COMPOUNDS OF POLYNYCLEOTIDE REPEAT-ASSOCIATED RNA-FOCI - ÉTUDE PRÉCLINIQUE DE COMPOSÉS PHARMACOLOGIQUES POUR LA TRAITEMENT DE LA DYSTROPHIE MUSCULAIRE
ÉTUDE PRÉ-CLINIQUE DE COMPOSÉS PHARMACOLOGIQUES POUR LE TRAITEMENT DE LA DYSTROPHIE MYOTONIQUE
STUDYING TELOMERASE ACTIVITY AND REGULATION IN SINGLE CANCER CELLS
CHARACTERIZATION OF CHEMICAL COMPOUNDS WHICH DISRUPT NUCLEAR CUG-RICH RNA FOCI IN DM1
TELOMERASE TRAFFICKING AND MAINTENANCE OF GENOME INTEGRITY
PATHOGENESIS OF MYOTONIC DYSTROPHY
LA LEVURE COMME SYSTEME MODELE POUR ETUDIER LA LOCALISATION ET LA REGULATION TRADUCTIONNELLE DES ARNM
TELOMERASE TRAFFICKING AND MAINTENANCE OF GENOME INTEGRITY
HIGH PERFORMANCE IMAGING AND IMAGE ANALYSIS UNIT
Outreach
Publications and presentations
Publications
- Laprade H., Querido E., Smith MJ., Guérit D., Crimmins H., Conomos D., Pourret E., Chartrand P., Sfeir A. (2020) Single-molecule imaging of telomerase RNA reveals a Recruitment – Retention model for telomere elongation. Molecular Cell, 79: 115-126.
- Lalonde M., Chartrand P. (2020) TERRA, a multifaceted regulator of telomerase activity at telomeres. Journal of Molecular Biology, 432: 4232-4243.
- Avogaro L., Querido E., Dalachi M., Jantsch MF., Chartrand P., Cusanelli E. (2018) Live-cell imaging reveals the dynamics and function of single-telomere TERRA molecules in cancer cells. RNA Biology, 15: 787-796.
- Ouenzar F., Lalonde M., Laprade H., Morin G., Gallardo F., Chartrand P. (2017) Cell cycle-dependent spatial segregation of telomerase RNA from sites of DNA damage. J. Cell Biology, 216: 2355-2371
- Moradi-Fard S., Sarthi J., Tittel-Elmer M., Lalonde M., Cusanelli E., Chartrand P., Cobb JA. (2016) Smc5/6 is a Telomere-associated complex that regulates Sir4 binding and TPE. PLoS Genetics. 12 e1006268.
- Cusanelli E., Chartrand P. (2015) Telomeric repeat-containing RNA TERRA: a noncoding RNA connecting telomere biology to genome integrity. Frontier in Genetics, 6: 143
- Shahbabian, K., Jeronimo, C., Forget, A., Robert, F., Chartrand, P. (2014) Co-transcriptional recruitment of Puf6 by She2 couples translational repression to mRNA localization. Nucleic Acids Research, 42: 8692-8704.
- Cusanelli E., Perez Romero, C.A., Chartrand P. (2013) Telomeric non-coding RNA nucleates telomerase clusters at short telomeres. Molecular Cell, 51: 780-791.
- Pfingsten, J.S., Goodrich, K.J., Taabazuing, C., Ouenzar, F., Chartrand, P., Cech T.R. (2012) Mutually exclusive binding of telomerase RNA and DNA by yeast Ku: a new model for telomerase recruitment. Cell. 148: 922-932.
- Querido E., Gallardo F., Beaudoin M., Ménard C., Chartrand P. (2011) Stochastic and reversible aggregation of mRNA with expanded CUG-triplet repeats. J. Cell Science. 124: 1703-1714.
- Gallardo F., Laterreur N., Cusanelli E., Ouenzar F., Querido E., Wellinger R.J., Chartrand P. (2011) Live cell imaging of telomerase RNA dynamics reveals cell cycle-dependent clustering of telomerase at elongating telomeres. Molecular Cell,44: 819-827.
- Shen Z., St-Denis, A., Chartrand P. (2010) Cotranscriptional recruitment of She2p by RNA pol II elongation factor Spt4-Spt5/DSIF promotes mRNA localization to yeast bud. Genes & Development, 24: 1914-1926
- Shen Z., Paquin N., Forget A., Chartrand P. (2009) Nuclear shuttling of She2p couples ASH1 mRNA localization to its translational repression by recruiting Loc1p and Puf6p. Mol. Biol. Cell, 20: 2265-2275.
- Gallardo F., Olivier C., Dandjinou A.T., Wellinger R.J., Chartrand P. (2008) TLC1 RNA nucleo-cytoplasmic trafficking links telomerase biogenesis to its recruitment to telomeres. The Embo J., 27: 748-757.
- Paquin N., Chartrand P. (2008) Local regulation of mRNA translation: new insights from the bud. Trends in Cell Biology, 18: 105-111.
- Paquin N., Ménade M., Poirier G., Donato D., Drouet E., Chartrand P. (2007) Local activation of yeast ASH1 mRNA translation through phosphorylation of Khd1p by the casein kinase Yck1p. Molecular Cell., 26: 795-809.
- Sylvestre Y., De Guire V., Querido E., Mukhopadhyay U.K., Bourdeau V., Major F., Ferbeyre G., Chartrand P. (2007) An E2F/miR-20a auto-regulatory feed-back loop. J. Biol. Chem., 282: 2135-2143.
- Olivier C., Poirier G., Gendron P., Boisgontier A., Major F., Chartrand P. (2005) Identification of a conserved RNA motif essential for She2p recognition and mRNA localization to the yeast bud. Mol. Cell. Biol. 25: 4752-4766.
Disciplines
- Biochemistry
- Molecular Biology
- Cell Biology
Areas of expertise
- Nucleic Acids
- Cell
- Chromosome (Living Organisms)
- Enzymes and Proteins
- Gene (Living Organisms)
- Macromolecules
- Biological and Biochemical Mechanisms
- Telomeres
- Neuromuscular Diseases