Transcribing RNA polymerase

Benoit Coulombe, PhD

Director, Department of Translational Proteomics, IRCM

Bell-Bombardier Research Chair, IRCM

Professor, Department of Biochemistry & Molecular Medicine, U of Montréal

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Our lab is harnessing the power of recombinant antibody- and mass spectrometry-based proteomics to map protein/gene expression programs at single-cell resolution in health and disease

 

We are part of the 37TrillionCells Initiative

The 37TrillionCells Initiative

Our goal is to integrate single-cell (sc) proteomics to sc transcriptomics and sc epigenomics to track, understand and target human cells at different stages of disease progression, and analyse their response to drug treatment. We seek to characterize modulations of gene expression programs that accompany deviations of cell trajectories from health to disease. Our focus is currently on leukodystrophies, COVID-19, Alzheimer’s, cardiometabolic conditions and cancer.

For the past decades, technical limitations have forced scientists to focus their analysis of the transcriptome on measurements made on cell populations that can mask significant differences between individual cells. With the development of single-cell RNA-seq, it is now possible to profile the transcriptome of individual cells with unprecedented depth and thereby uncover, transcriptome-wide, the heterogeneity that exists within these populations. As a consequence, the specific function of each individual cell can be revealed. Because proteins are more often directly involved in gene regulation, single-cell proteome profiling represents a main challenge that also faces technical limitations, as mass spectrometry is currently not sensitive enough to profile the proteome of individual cells. Alternative proteomic methods are needed to overcome this important challenge.

Our group adopts a resolutely innovative modus operandi, which contributes to shaking up our classic methods by creating a transdisciplinary and open ecosystem where totally distinct approaches collide to allow both the study of the atomic structure of proteins and their organization in complex networks, both the analysis of microscopic model systems and of patient cohorts, both the screening of small molecules and their development to create affordable drugs.

To join the Coulombe lab as a graduate student or a postdoctoral fellow, please send a motivation letter and a complete CV by email directly to Benoit.Coulombe@ircm.qc.ca. Only candidates of interest will be contacted.

10 MOST SIGNIFICANT DISCOVERIES FROM OUR LAB

1998: The Promoter DNA Wrapping Model

Robert F, Douziech M, Forget D, Egly JM, Greenblatt J, Burton ZF, Coulombe B.

Wrapping of promoter DNA around the RNA polymerase II initiation complex induced by TFIIF.

Mol Cell. 1998 Sep;2(3):341-51.

2007: The RNA polymerase II interactome and RNA Polymerase II-Associated Proteins (RPAPs)

Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Thérien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B.

Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme.

Mol Cell. 2007 Jul 20;27(2):262-74.

2013: A Novel Family of Lysine Methyltransferases That Target Molecular Chaperones

Cloutier P, Lavallée-Adam M, Faubert D, Blanchette M, Coulombe B.

A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.

PLoS Genet. 2013;9(1):e1003210.

2015: Leukodystrophy-Causing Mutations Impair RNA polymerase III Biogenesis

Thiffault I, Wolf NI, Forget D, Guerrero K, Tran LT, Choquet K, Lavallée-Adam M, Poitras C, Brais B, Yoon G, Sztriha L, Webster RI, Timmann D, van de Warrenburg BP, Seeger J, Zimmermann A, Máté A, Goizet C, Fung E, van der Knaap MS, Fribourg S, Vanderver A, Simons C, Taft RJ, Yates JR 3rd, Coulombe B, Bernard G.

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.

Nat Commun. 2015 Jul 7;6:7623.

2017: The R2TP/PFD-like Complex Regulates Assembly of the U5 snRNP and TSC complex

Cloutier P, Poitras C, Durand M, Hekmat O, Fiola-Masson É, Bouchard A, Faubert D, Chabot B, Coulombe B.

R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein.

Nat Commun. 2017 May 31;8:15615.

2018: The Particle for Arrangement of Quaternary structure (PAQosome)

Houry WA, Bertrand E, Coulombe B.

The PAQosome, an R2TP-Based Chaperone for Quaternary Structure Formation.

Trends Biochem Sci. 2018 Jan;43(1):4-9.

2018: A Model for Interactome Wiring by the PAQosome

Coulombe B, Cloutier P, Gauthier MS.

How do our cells build their protein interactome?

Nat Commun. 2018 Jul 27;9(1):2955.

2018: Phosphorylated PCSK9 Is a Potent Biomarker for Various Diseases

Gauthier MS, Awan Z, Bouchard A, Champagne J, Tessier S, Faubert D, Chabot K, Garneau PY, Rabasa-Lhoret R, Seidah NG, Ridker PM, Genest J, Coulombe B.

Posttranslational modification of proprotein convertase subtilisin/kexin type 9 is differentially regulated in response to distinct cardiometabolic treatments as revealed by targeted proteomics.

J Clin Lipidol. 2018 Jul-Aug;12(4):1027-1038.

2020: Complete Subunit Composition of the PAQosome

Cloutier P, Poitras C, Faubert D, Bouchard A, Blanchette M, Gauthier MS, Coulombe B.

Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subunit of the PAQosome.

J Proteome Res. 2020 Jan 3;19(1):18-27.

2021: Mutations in POLR3B cause ataxia, spasticity and demyelinating neuropathy, and impair RNA polymerase III assembly

Djurdja Djordjevic, Maxime Pinard, Marie-Soleil Gauthier, Constance Smith-Hicks, Trevor L. Hoffman, Nicole I. Wolf, Renske Oegema, Ellen van Binsbergen, Berivan Baskin, Geneviève Bernard, Sébastien Fribourg, Benoit Coulombe, Grace Yoon.

De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy.

The American Journal of Human Genetics. 2021 Jan 7; 186–193.

 
 

TEAM

Dr. Benoit Coulombe
Dr. Benoit Coulombe
Director
Dr. Marie-Soleil Gauthier
Dr. Marie-Soleil Gauthier
Senior Associate Researcher
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Dr. Maxime Pinard
Associate Researcher
esen_sokullu.png
Dr. Esen Sokullu
Postdoctoral Fellow
Asmae_Moursli_small.png
Asmae Moursli
PhD student
Christian Poitras
Christian Poitras
Systems Analyst
Alexa Derksen
Alexa Derksen
Master Degree Student (Dr. G. Bernard)
Golden Marble
Vijaya Madhoo
Administrative Assistant
Diane Forget
Diane Forget
Honorary Lab Member

2020-06-26 :

Diane Forget prend sa retraite après 27 ans de service dévoué pour le laboratoire. Elle a eu une contribution exceptionnelle pour nos publications, la formation de personnel, l'administration des fonds de recherche et la planification des espaces de laboratoire. Avec toute notre reconnaissance, merci et bonne continuation.

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