Trained as a biochemist (UQAM, 1989), and as a molecular and cellular biologist (U. of Montreal 1996 and Karolinska Institutet, Stockholm, Sweden, 2001), Dr. Patrick Provost is a Full Professor in the Department of Microbiology, Infectious diseases and Immunology at the Faculty of Medicine of Université Laval, and a Researcher at the CHU de Québec Research Center/CHUL Pavilion since 2001. To date, the turning point in his career has been his co-discovery, in 2002, of the ribonuclease Dicer in humans. This enzyme catalyzes the formation of microRNAs (19 to 24 nucleotides long), which are now recognized as key regulators of ~60% of the genes in humans.
His current research aims to improve our understanding of the molecular mechanisms underlying the biogenesis, function and transfer of small non-coding RNAs (e. g. microRNAs) between cells and species through extracellular vesicles (EVs; 0.1-1 µm in diameter) in the context of health, nutrition and disease.
His work has been regularly covered by the media, given their importance and translational nature.
Content and therapeutic applications of extracellular vesicles (EVs) in milk
EVs are released from a wide variety of cells in body fluids, including milk. The analysis of cow’s milk intended for human consumption revealed that it contains a new type of EVs, which carries most of the microRNAs (Benmoussa et al., J. Extracell. Vesicles 2017; PMID: 29904572) and is able to protect their microRNAs from degradation during simulated digestion (i. e. under the biophysical, chemical and biochemical conditions prevailing in the human gastrointestinal tract) (Benmoussa et al., J. Nutr. 2016; PMID: 27708120).
We also determined that these EVs isolated from milk were enriched with anti-inflammatory proteins, such as epidermal growth factor 8 (MFG-E8) (Benmoussa et al., J. Proteomics 2019; PMID: 30153512).
These results prompted us to explore the therapeutic potential of milk EVs under inflammatory conditions affecting the gastrointestinal tract.
A unique model to evaluate the oral transfer of dietary microRNAs
It has long been believed that the genetic material (e. g. microRNAs) in food is rapidly degraded during digestion. However, we have demonstrated that microRNAs in cow’s milk intended for human consumption are bioaccessible, partly due to the protective effects of EVs. The ability of milk EVs to protect their labile cargo of bioactive molecules during digestion opens the way for the possible oral transfer of dietary microRNAs. This possibility will be verified through a unique model, which, combined with advanced techniques and approaches, will allow us to confirm (or invalidate) the oral transfer of milk microRNAs.
A new class of small non-coding RNAs
At the heart of the genetic information that flows through our cells (DNA is transcribed into RNA, which is translated into proteins), small species of RNA that do not code for proteins, such as microRNAs (19 to 24 nucleotides (nt) long), are now recognized as key regulators of gene expression.
Contrary to the current scientific dogma, according to which there is no endogenous RNA shorter than 16 nt that can be biologically relevant, we have serendipitously discovered a 12-nt RNA species capable of competing with microRNA regulation of mRNA translation into proteins in human cells (Plante et al., Front. Genet. 2012; PMID: 22675332).
More extensive and in-depth analyses have enabled us to identify a new class of small non-coding RNAs. Our current research aims to elucidate the biogenesis pathway and effector ribonucleoprotein complexes involved in the role and function of these small non-coding RNAs in human and mouse cells.
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ago1 and dcr1, two core components of the RNA interference pathway, functionally diverge from rdp1 in regulating cell cycle events in Schizosaccharomyces pombe.Journal Article
Mol Biol Cell, 15 (3), pp. 1425-35, 2004, ISSN: 1059-1524.
Resistance of human hepatitis delta virus RNAs to dicer activity.Journal Article
J Virol, 77 (22), pp. 11910-7, 2003, ISSN: 0022-538X.
The nuclear RNase III Drosha initiates microRNA processing.Journal Article
Nature, 425 (6956), pp. 415-9, 2003, ISSN: 0028-0836.
Dicer is required for chromosome segregation and gene silencing in fission yeast cells.Journal Article
Proc Natl Acad Sci U S A, 99 (26), pp. 16648-53, 2002, ISSN: 0027-8424.
Ribonuclease activity and RNA binding of recombinant human Dicer.Journal Article
EMBO J, 21 (21), pp. 5864-74, 2002, ISSN: 0261-4189.
Molecular cloning and functional characterization of mouse coactosin-like protein.Journal Article
Biochem Biophys Res Commun, 290 (2), pp. 783-9, 2002, ISSN: 0006-291X.
Coactosin-like protein, a human F-actin-binding protein: critical role of lysine-75.Journal Article
Biochem J, 359 (Pt 2), pp. 255-63, 2001, ISSN: 0264-6021.
5-Lipoxygenase interacts with coactosin-like protein.Journal Article
J Biol Chem, 276 (19), pp. 16520-7, 2001, ISSN: 0021-9258.
The N-terminal domain of 5-lipoxygenase binds calcium and mediates calcium stimulation of enzyme activity.Journal Article
J Biol Chem, 275 (49), pp. 38787-93, 2000, ISSN: 0021-9258.
Interaction of 5-lipoxygenase with cellular proteins.Journal Article
Proc Natl Acad Sci U S A, 96 (5), pp. 1881-5, 1999, ISSN: 0027-8424.
- A novel class of small non-coding RNAs, Subvention, Conseil de recherches en sciences naturelles et génie Canada, Subventions à la découverte SD (individuelles et d'équipe), from 2019-04-01 to 2024-03-31
- A unique model to assess the oral transfer of dietary microRNAs, Subvention, Instituts de recherche en santé du Canada, Subvention Projet, from 2019-10-01 to 2022-09-30
- Centre de recherche du CHU de Québec - Université Laval, Subvention, Centre hospitalier universitaire de Québec - Université Laval, Centres de recherche affiliés, from 2017-01-01 to 2099-12-31