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Article: Protein components of the microRNA pathway and human diseases.

Perron, Marjorie P / Provost, Patrick

Methods in molecular biology (Clifton, N.J.)

2009 Volume 487, Page(s) 369–385

Abstract: MicroRNAs (miRNAs) are key regulators of messenger RNA (mRNA) translation known to be involved in a wide variety of cellular processes. In fact, their individual importance is reflected in the diseases that may arise upon the loss, mutation or ... ...

Abstract	MicroRNAs (miRNAs) are key regulators of messenger RNA (mRNA) translation known to be involved in a wide variety of cellular processes. In fact, their individual importance is reflected in the diseases that may arise upon the loss, mutation or dysfunction of specific miRNAs. It has been appreciated only recently that diseases may also develop when the protein components of the miRNA machinery itself are affected. The core enzymes of the major protein complexes involved in miRNA biogenesis and function, such as the ribonucleases III (RNases III) Drosha and Dicer as well as Argonaute 2 (Ago2), appear to be essential. However, the accessory proteins of the miRNA pathway, such as the DiGeorge syndrome critical region gene 8 (DGCR8) protein, Exportin-5 (Exp-5), TAR RNA binding protein (TRBP) and fragile X mental retardation protein (FMRP), are each related, in various ways, to specific genetic diseases.
MeSH term(s)	Gene Silencing ; Genetic Diseases, Inborn/metabolism ; Genetic Diseases, Inborn/therapy ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Proteins/metabolism
Chemical Substances	MicroRNAs ; Proteins
Language	English
Publishing date	2009-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1064-3745
ISSN	1064-3745
DOI	10.1007/978-1-60327-547-7_18
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Article ; Online: Regulation of human Dicer by the resident ER membrane protein CLIMP-63.

Pépin, Geneviève / Perron, Marjorie P / Provost, Patrick

Nucleic acids research

2012 Volume 40, Issue 22, Page(s) 11603–11617

Abstract: The ribonuclease Dicer plays a central role in the microRNA pathway by catalyzing the formation of microRNAs, which are known to regulate messenger RNA (mRNA) translation. In order to improve our understanding of the molecular context in which Dicer ... ...

Abstract	The ribonuclease Dicer plays a central role in the microRNA pathway by catalyzing the formation of microRNAs, which are known to regulate messenger RNA (mRNA) translation. In order to improve our understanding of the molecular context in which Dicer functions and how it is regulated in human cells, we sought to expand its protein interaction network by employing a yeast two-hybrid screening strategy. This approach led to the identification and characterization of cytoskeleton-linking endoplasmic reticulum (ER) membrane protein of 63 kDa (CLIMP-63) as a novel Dicer-interacting protein. CLIMP-63 interacts with Dicer to form a high molecular weight complex, which is electrostatic in nature, is not mediated by RNA and is catalytically active in pre-microRNA processing. CLIMP-63 is required for stabilizing Dicer protein and for optimal regulation of a reporter gene coupled to the 3' untranslated region of HMGA2 mRNA in human cells. Interacting with a portion of the luminal domain of CLIMP-63 and within minutes of its synthesis, our results suggest that Dicer transits through the ER, is glycosylated and can be secreted by cultured human cells with CLIMP-63. Our findings define CLIMP-63 as a novel protein interactor and regulator of Dicer function, involved in maintaining Dicer protein levels in human cells.
MeSH term(s)	DEAD-box RNA Helicases/biosynthesis ; DEAD-box RNA Helicases/chemistry ; DEAD-box RNA Helicases/metabolism ; Endoplasmic Reticulum/enzymology ; Enzyme Stability ; Glycosylation ; HEK293 Cells ; HeLa Cells ; Humans ; Membrane Proteins/metabolism ; MicroRNAs/metabolism ; Protein Interaction Domains and Motifs ; RNA Interference ; RNA Precursors/metabolism ; RNA Processing, Post-Transcriptional ; Ribonuclease III/biosynthesis ; Ribonuclease III/chemistry ; Ribonuclease III/metabolism
Chemical Substances	CKAP4 protein, human ; Membrane Proteins ; MicroRNAs ; RNA Precursors ; DICER1 protein, human (EC 3.1.26.3) ; Ribonuclease III (EC 3.1.26.3) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2012-10-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gks903
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Article: Protein interactions and complexes in human microRNA biogenesis and function.

Perron, Marjorie P / Provost, Patrick

Frontiers in bioscience : a journal and virtual library

2008 Volume 13, Page(s) 2537–2547

Abstract: ... repressing its translation, the miRNP-silenced mRNA is directed to the P-bodies, where the mRNA is ...

Abstract	Encoded in the genome of most eukaryotes, microRNAs (miRNAs) have been proposed to regulate specifically up to 90% of human genes through a process known as miRNA-guided RNA silencing. The aim of this review is to present this process as the integration of a succession of specialized molecular machines exerting well defined functions. The nuclear microprocessor complex initially recognizes and processes its primary miRNA substrate into a miRNA precursor (pre-miRNA). This structure is then exported to the cytoplasm by the Exportin-5 complex where it is presented to the pre-miRNA processing complex. Following pre-miRNA conversion into a miRNA:miRNA* duplex, this complex is assembled into a miRNA-containing ribonucleoprotein (miRNP) complex, after which the miRNA strand is selected. The degree of complementarity of the miRNA for its messenger RNA (mRNA) target guides the recruitment of the miRNP complex. Initially repressing its translation, the miRNP-silenced mRNA is directed to the P-bodies, where the mRNA is either released from its inhibition upon a cellular signal and/or actively degraded. The potency and specificity of miRNA biogenesis and function rely on the distinct protein x protein, protein x RNA and RNA:RNA interactions found in different complexes, each of which fulfill a specific function in a well orchestrated process.
MeSH term(s)	Animals ; Argonaute Proteins ; DiGeorge Syndrome/genetics ; Eukaryotic Initiation Factor-2/metabolism ; Gene Silencing ; Humans ; Karyopherins/metabolism ; MicroRNAs/chemistry ; MicroRNAs/metabolism ; Models, Biological ; Protein Interaction Mapping ; Proteins/chemistry ; RNA, Small Interfering/metabolism ; RNA-Binding Proteins/metabolism ; Ribonuclease III/metabolism
Chemical Substances	AGO2 protein, human ; Argonaute Proteins ; Eukaryotic Initiation Factor-2 ; Karyopherins ; MicroRNAs ; Proteins ; RNA, Small Interfering ; RNA-Binding Proteins ; XPO5 protein, human ; trans-activation responsive RNA-binding protein (136628-24-5) ; Ribonuclease III (EC 3.1.26.3)
Language	English
Publishing date	2008-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2141320-4
ISSN	1093-9946
ISSN	1093-9946
DOI	10.2741/2865
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Article ; Online: Detection of human Dicer and Argonaute 2 catalytic activity.

Perron, Marjorie P / Landry, Patricia / Plante, Isabelle / Provost, Patrick

Methods in molecular biology (Clifton, N.J.)

2011 Volume 725, Page(s) 121–141

Abstract: The microRNA (miRNA)-guided RNA silencing pathway is a central and well-defined cellular process involved in messenger RNA (mRNA) translational control. This complex regulatory process is achieved by a well orchestrated machinery composed of a relatively ...

Abstract	The microRNA (miRNA)-guided RNA silencing pathway is a central and well-defined cellular process involved in messenger RNA (mRNA) translational control. This complex regulatory process is achieved by a well orchestrated machinery composed of a relatively few protein components, among which the ribonuclease III (RNase III) Dicer and Argonaute 2 (Ago2) play a central role. These two proteins are essential and it is of particular interest to measure and detect their catalytic activity under various situations and/or conditions. In this chapter, we describe different protocols that aim to study and determine the catalytic activity of Dicer and Ago2 in cell extracts, immune complexes, and size-fractionated cell extracts. Another protocol aimed at assessing miRNA binding to Ago2 is also described. These experimental approaches are likely to be useful to researchers investigating the main steps of miRNA biogenesis and function in human health and diseases.
MeSH term(s)	Argonaute Proteins ; Blotting, Northern ; Catalysis ; Cell Line ; Denaturing Gradient Gel Electrophoresis ; Enzyme Assays ; Eukaryotic Initiation Factor-2/metabolism ; HEK293 Cells ; Humans ; Isotope Labeling ; MicroRNAs/metabolism ; Protein Binding ; RNA/genetics ; RNA/metabolism ; Ribonuclease III/metabolism ; Subcellular Fractions/metabolism ; Transcription, Genetic/genetics
Chemical Substances	AGO2 protein, human ; Argonaute Proteins ; Eukaryotic Initiation Factor-2 ; MicroRNAs ; RNA (63231-63-0) ; Ribonuclease III (EC 3.1.26.3)
Language	English
Publishing date	2011-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-61779-046-1_9
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Article: The Saccharomyces cerevisiae Arf3 protein is involved in actin cable and cortical patch formation.

Lambert, Alexandra A / Perron, Marjorie P / Lavoie, Elyse / Pallotta, Dominick

FEMS yeast research

2007 Volume 7, Issue 6, Page(s) 782–795

Abstract: We show that Arf3p, a member of the ADP ribosylation family, is involved in the organization of actin cables and cortical patches in Saccharomyces cerevisiae. Profilin-deficient cells (pfy1Delta) have severe growth defects and lack actin cables. ... ...

Abstract	We show that Arf3p, a member of the ADP ribosylation family, is involved in the organization of actin cables and cortical patches in Saccharomyces cerevisiae. Profilin-deficient cells (pfy1Delta) have severe growth defects and lack actin cables. Overexpression of ARF3 restores actin cables and corrects growth defects in these cells. Cells deficient for the cortical patch proteins Las17p and Vrp1p have growth defects and a random cortical patch distribution. Overexpression of ARF3 in las17Delta and in vrp1Delta cells partially corrects growth defects and restores the polarized distribution of cortical patches. The N-terminal glycine, a myristoylation site in Arf3p, is necessary for its suppressor activity. arf3Delta cells show a random budding pattern. Overexpression of BNI1, GEA2 or SYP1, three genes involved in actin cytoskeleton formation, restores the normal axial budding pattern of arf3Delta cells. BUD6 is a polarity gene and GEA2 is involved in retrograde transport and the organization of the actin cytoskeleton. We have identified genetic interactions between ARF3 and BUD6, and between ARF3 and GEA2. Both double mutant strains have actin cytoskeleton defects. Our results support a role for ARF3 in cell polarity and the organization of the actin cytoskeleton.
MeSH term(s)	ADP-Ribosylation Factors/genetics ; ADP-Ribosylation Factors/metabolism ; Actins/metabolism ; Cytoskeleton/metabolism ; Gene Expression ; Glycine/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	Actins ; Saccharomyces cerevisiae Proteins ; ARF3 protein, S cerevisiae (EC 3.6.1.-) ; ADP-Ribosylation Factors (EC 3.6.5.2) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2007-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2036775-2
ISSN	1567-1364 ; 1567-1356
ISSN (online)	1567-1364
ISSN	1567-1356
DOI	10.1111/j.1567-1364.2007.00239.x
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Article ; Online: A Single-Center 18-Year Series of 73 Cases of Metaplastic Carcinoma of the Breast

Kassandra Thériault / Mariem Ben Moussa / Marjorie Perron / Christine Desbiens / Brigitte Poirier / Éric Poirier / Dominique Leblanc / Claudya Morin / Julie Lemieux / Jean-Charles Hogue / Dominique Boudreau

The Breast Journal, Vol

2024 Volume 2024

Abstract: ... setting, had a significant positive effect on 5-year OS (P=0.003) and 5-year DFS (P=0.004). Nodal ... involvement was associated with worse OS (P=0.049) but similar DFS (P=0.157). Lumpectomy was associated ... with better 5-year OS (P<0.0001) and DFS (P=0.0002) compared with mastectomy. Conclusion. MeBC represents ...

Abstract	Aim. To examine the clinical management of metaplastic breast cancer (MeBC), particularly the role of chemotherapy. Methods. This retrospective study included patients with MeBC (n = 73) from a tertiary breast cancer center: the “Centre des Maladies du Sein of the CHU de Québec–Université Laval.” The specimens were reviewed by two pathologists. Patient and tumor characteristics, systemic therapy (neoadjuvant and adjuvant), disease-free survival (DFS), and overall survival (OS) were recorded. Results. The median follow-up was 57.2 months. The mean tumor size was 39.5 ± 32.1 (range, 1–200) mm. Most were in grade 3 (75.3%), without evidence of clinical nodal involvement (75.3%), and triple-negative (79.5%). Chemotherapy was given to 49 (67.1%) patients. Thirty-seven patients (50.7%) underwent a mastectomy, and 22/37 (59.5%) received radiotherapy. Adjuvant chemotherapy was given to 36 patients (49.3%), and nine (12.3%) patients were treated with neoadjuvant chemotherapy. The 5-year OS and DFS rates were 60.2% and 66.8%. Among the nine patients who received neoadjuvant chemotherapy, three (33.3%) achieved a partial response, three (33.3%) had stable disease, and three (33.3%) had disease progression. The use of chemotherapy, especially in the adjuvant setting, had a significant positive effect on 5-year OS (P=0.003) and 5-year DFS (P=0.004). Nodal involvement was associated with worse OS (P=0.049) but similar DFS (P=0.157). Lumpectomy was associated with better 5-year OS (P<0.0001) and DFS (P=0.0002) compared with mastectomy. Conclusion. MeBC represents a rare heterogeneous group of malignancies with poor prognosis. Adjuvant chemotherapy was associated with improved OS and DFS. Patients should be carefully selected for neoadjuvant chemotherapy.
Keywords	Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Hindawi-Wiley
Document type	Article ; Online
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Article ; Online: Existence of a microRNA pathway in anucleate platelets.

Landry, Patricia / Plante, Isabelle / Ouellet, Dominique L / Perron, Marjorie P / Rousseau, Guy / Provost, Patrick

Nature structural & molecular biology

2009 Volume 16, Issue 9, Page(s) 961–966

Abstract: Platelets have a crucial role in the maintenance of hemostasis as well as in thrombosis and vessel occlusion, which underlie stroke and acute coronary syndromes. Anucleate platelets contain mRNAs and are capable of protein synthesis, raising the issue of ...

Abstract	Platelets have a crucial role in the maintenance of hemostasis as well as in thrombosis and vessel occlusion, which underlie stroke and acute coronary syndromes. Anucleate platelets contain mRNAs and are capable of protein synthesis, raising the issue of how these mRNAs are regulated. Here we show that human platelets harbor an abundant and diverse array of microRNAs (miRNAs), which are known as key regulators of mRNA translation in other cell types. Further analyses revealed that platelets contain the Dicer and Argonaute 2 (Ago2) complexes, which function in the processing of exogenous miRNA precursors and the control of specific reporter transcripts, respectively. Detection of the receptor P2Y(12) mRNA in Ago2 immunoprecipitates suggests that P2Y(12) expression may be subjected to miRNA control in human platelets. Our study lends an additional level of complexity to the control of gene expression in these anucleate elements of the cardiovascular system.
MeSH term(s)	Argonaute Proteins ; Base Sequence ; Blood Platelets/cytology ; Blood Platelets/metabolism ; Cardiovascular System/metabolism ; Cell Extracts/genetics ; Eukaryotic Initiation Factor-2/genetics ; Eukaryotic Initiation Factor-2/metabolism ; Gene Expression Regulation ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Protein Binding ; RNA Interference ; Receptors, Purinergic P2/genetics ; Receptors, Purinergic P2Y12
Chemical Substances	AGO2 protein, human ; Argonaute Proteins ; Cell Extracts ; Eukaryotic Initiation Factor-2 ; MicroRNAs ; P2RY12 protein, human ; Receptors, Purinergic P2 ; Receptors, Purinergic P2Y12
Language	English
Publishing date	2009-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126708-X
ISSN	1545-9985 ; 1545-9993
ISSN (online)	1545-9985
ISSN	1545-9993
DOI	10.1038/nsmb.1651
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Zs.A 4101: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Regulatory RNAs: future perspectives in diagnosis, prognosis, and individualized therapy.

Perron, Marjorie P / Boissonneault, Vincent / Gobeil, Lise-Andrée / Ouellet, Dominique L / Provost, Patrick

Methods in molecular biology (Clifton, N.J.)

2007 Volume 361, Page(s) 311–326

Abstract: With potentially up to 1000 microRNAs (miRNAs) present in the human genome, altogether regulating the expression of thousands of genes, one can anticipate that miRNAs will play a significant role in health and disease. Deregulated protein expression ... ...

Abstract	With potentially up to 1000 microRNAs (miRNAs) present in the human genome, altogether regulating the expression of thousands of genes, one can anticipate that miRNAs will play a significant role in health and disease. Deregulated protein expression induced by a dysfunctional miRNA-based regulatory system is thus expected to lead to the development of serious, if not lethal, genetic diseases. A relationship among miRNAs, Dicer, and cancer has recently been suggested. Further investigations will help establish specific causal links between dysfunctional miRNAs and diseases. miRNAs of foreign origin, e.g., viruses, may also be used as specific markers of viral infections. In these cases, miRNA expression profiles could represent a powerful diagnostic tool. Regulatory RNAs may also have therapeutic applications, by which disease-causing genes or viral miRNAs could be neutralized, or functional miRNAs be restored. Will bedside miRNA expression profiling eventually assist physicians in providing patients with accurate diagnosis, personalized therapy, and treatment outcome?
MeSH term(s)	Diagnosis, Differential ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Gene Expression Regulation, Viral/drug effects ; Gene Expression Regulation, Viral/genetics ; Genome, Human ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; MicroRNAs/therapeutic use ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Prognosis ; Virus Diseases/diagnosis ; Virus Diseases/drug therapy ; Virus Diseases/genetics ; Virus Diseases/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2007
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1064-3745
ISSN	1064-3745
DOI	10.1385/1-59745-208-4:311
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Article: MicroRNAs in gene regulation: when the smallest governs it all.

Ouellet, Dominique L / Perron, Marjorie P / Gobeil, Lise-Andrée / Plante, Pierre / Provost, Patrick

Journal of biomedicine & biotechnology

2006 Volume 2006, Issue 4, Page(s) 69616

Abstract: Encoded by the genome of most eukaryotes examined so far, microRNAs (miRNAs) are small approximately 21-nucleotide (nt) noncoding RNAs (ncRNAs) derived from a biosynthetic cascade involving sequential processing steps executed by the ribonucleases ( ... ...

Abstract	Encoded by the genome of most eukaryotes examined so far, microRNAs (miRNAs) are small approximately 21-nucleotide (nt) noncoding RNAs (ncRNAs) derived from a biosynthetic cascade involving sequential processing steps executed by the ribonucleases (RNases) III Drosha and Dicer. Following their recent identification, miRNAs have rapidly taken the center stage as key regulators of gene expression. In this review, we will summarize our current knowledge of the miRNA biosynthetic pathway and its protein components, as well as the processes it regulates via miRNAs, which are known to exert a variety of biological functions in eukaryotes. Although the relative importance of miRNAs remains to be fully appreciated, deregulated protein expression resulting from either dysfunctional miRNA biogenesis or abnormal miRNA-based gene regulation may represent a key etiologic factor in several, as yet unidentified, diseases. Hence is our need to better understand the complexity of the basic mechanisms underlying miRNA biogenesis and function.
Language	English
Publishing date	2006-10-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2052552-7
ISSN	1110-7251 ; 1110-7243
ISSN (online)	1110-7251
ISSN	1110-7243
DOI	10.1155/JBB/2006/69616
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Article ; Online: MicroRNAs in Gene Regulation

Dominique L. Ouellet / Marjorie P. Perron / Lise-Andrée Gobeil / Pierre Plante / Patrick Provost

Journal of Biomedicine and Biotechnology, Vol

When the Smallest Governs It All

2006 Volume 2006

Abstract: Encoded by the genome of most eukaryotes examined so far, microRNAs (miRNAs) are small ~21-nucleotide (nt) noncoding RNAs (ncRNAs) derived from a biosynthetic cascade involving sequential processing steps executed by the ribonucleases (RNases) III Drosha ...

Abstract	Encoded by the genome of most eukaryotes examined so far, microRNAs (miRNAs) are small ~21-nucleotide (nt) noncoding RNAs (ncRNAs) derived from a biosynthetic cascade involving sequential processing steps executed by the ribonucleases (RNases) III Drosha and Dicer. Following their recent identification, miRNAs have rapidly taken the center stage as key regulators of gene expression. In this review, we will summarize our current knowledge of the miRNA biosynthetic pathway and its protein components, as well as the processes it regulates via miRNAs, which are known to exert a variety of biological functions in eukaryotes. Although the relative importance of miRNAs remains to be fully appreciated, deregulated protein expression resulting from either dysfunctional miRNA biogenesis or abnormal miRNA-based gene regulation may represent a key etiologic factor in several, as yet unidentified, diseases. Hence is our need to better understand the complexity of the basic mechanisms underlying miRNA biogenesis and function.
Keywords	Biotechnology ; TP248.13-248.65 ; Medicine ; R
Subject code	500
Language	English
Publishing date	2006-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
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