Emmanuel Labourier

Massachusetts General Hospital

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Jamal Tazi

Abivax (France)

Walairat Laosinchai-Wolf

Asuragen (United States)

Anna E. Szafranska

Asuragen (United States)

Sylvie Beaudenon‐Huibregtse

High Throughput Biology (United States)

Martina Doleshal

Asuragen (United States)

Claude Brunel

Centre National de la Recherche Scientifique

Jaclyn Shingara

Asuragen (United States)

Etienne Antoine

Université de Montpellier

Imed‐Eddine Gallouzi

McGill University

Eric Allemand

Inserm

Cooperative Institutions

The University of Texas MD Anderson Cancer Center

Massachusetts General Hospital

Università Cattolica del Sacro Cuore

Beth Israel Deaconess Medical Center

Faculty of Media

John Wiley & Sons (United States)

Charles River Laboratories (Netherlands)

Centre National de la Recherche Scientifique

Asuragen (United States)

Inserm

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Purification of Drosophila snRNPs and characterization of two populations of functional U1 particles

RNA (2001)

Emmanuel Labourier Donald C. Rio

U1 snRNP is required at an early stage during assembly of the spliceosome, the dynamic ribonucleoprotein (RNP) complex that performs nuclear pre-mRNA splicing. Here, we report the purification of U1 snRNP particles from Drosophila nuclear extracts and the characterization of their biochemical properties, polypeptide contents, and splicing activities. On the basis of their antigenicity, apparent molecular weight, and by peptide sequencing, the Drosophila 70K, SNF, B, U1-C, D1, D2, D3, E, F, and G proteins are shown to be integral components of these particles. Sequence database searches revealed that both the U1-specific and the Sm proteins are extensively conserved between human and Drosophila snRNPs. Furthermore, both species possess a conserved intrinsic U1-associated kinase activity with identical substrate specificity in vitro. Finally, our results demonstrate that a second type of functional U1 particle, completely lacking the U1/U2-specific protein SNF and the associated protein kinase activity, can be isolated from cultured Kc cell or Canton S embryonic nuclear extracts. This work describes the first characterization of a purified Drosophila snRNP particle and reinforces the view that their activity and composition, with the exception of the atypical bifunctional U1-A/U2-B″ SNF protein, are highly conserved in metazoans.

snRNP

Small nuclear ribonucleoprotein

Spliceosome

Small nuclear RNA

Conserved sequence

10.1017/s1355838201001327

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Citations (9)

Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages

BMC Genomics (2011)

Rubén Rangel-Salazar Marie Lindholm Carlos A. Aguilar‐Salinas Yolanda Alvarado‐Caudillo Kristina B. V. Døssing

Abstract Background We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these epigenetic responses; 2) test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Results Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1) surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2) independent of the Dicer/micro-RNA pathway. Conclusions Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

DNA methyltransferase

Dicer

DNMT1

Histone Methylation

10.1186/1471-2164-12-582

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Citations (38)

Abstract #1095: Accurate Detection of Oncogenic Mutations in Thyroid Nodule Aspirates with the Next Generation Sequencing Thygenx Test

Endocrine Practice (2015)

Emmanuel Labourier Joanna W. Song-Yang Arun Timmaraju Gyanendra Kumar Seiyu Hosono

Nodule (geology)

Thyroid Nodules

10.1016/s1530-891x(20)42405-x

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Citations (1)

Accurate Molecular Characterization of Formalin-Fixed, Paraffin-Embedded Tissues by microRNA Expression Profiling

Journal of Molecular Diagnostics (2008)

Anna E. Szafranska Timothy S. Davison Jaclyn Shingara Martina Doleshal Judith A. Riggenbach

Profiling (computer programming)

10.2353/jmoldx.2008.080018

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Citations (119)

Quantitative Multiplex Measurement of BCR-ABL1 Expression on the International Scale Using the BCR/ABL1 Quant™ RUO Reagents and the LightCycler® 480

Blood (2011)

Justin T. Brown Walairat Laosinchai-Wolf Emmanuel Labourier Philip J Ginsburg Thomas B. Ryder

Multiplex

breakpoint cluster region

ABL

10.1182/blood.v118.21.4430.4430

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Conversion, Correction, and International Scale Standardization: Results From a Multicenter External Quality Assessment Study forBCR-ABL1Testing

Archives of Pathology & Laboratory Medicine (2014)

Mike Griffiths Simon Patton Alberto Grossi J. P. Clark Maria F. Paz

Monitoring BCR-ABL1 expression levels relative to clinically validated response criteria on the International Scale (IS) is vital in the optimal management of patients with chronic myeloid leukemia, yet significant variability remains across laboratories worldwide.To assess method performance, interlaboratory precision, and different IS standardization modalities in representative laboratories performing routine BCR-ABL1 testing.Fifteen blinded test specimens with 5-level nominal BCR-ABL1 to ABL1 IS percentage ratios ranging from 5% to 0.0005% and 4-level secondary IS reference panels, the ARQ IS Calibrator Panels, were tested by relative quantitative polymerase chain reaction in 15 laboratories in 5 countries. Both raw and IS percentage ratios calculated by using local conversion factors (CFs) or analytic correction parameters (CPs) were collected and analyzed.A total of 670 valid positive results were generated. BCR-ABL1 detection was associated with variable ABL1 quality metric passing rates (P < .001) and reached at least 0.01% in 13 laboratories. Intralaboratory precision was within 2.5-fold for all sample levels combined with a relative mean difference greater than 5-fold across laboratories. International Scale accuracy was increased by using both the CF and CP standardization methods. Classification agreement for major molecular response status was 90% after CF conversion and 93% after CP correction, with precision improved by 3-fold for the CP method.Despite preanalytic and analytic differences between laboratories, conversion and correction are effective IS standardization methods. Validated secondary reference materials can facilitate global diffusion of the IS without the need to perform sample exchange and improve the accuracy and precision of BCR-ABL1 quantitative measurements, including at low levels of residual disease.

10.5858/arpa.2013-0754-oa

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Citations (4)

A MicroRNA-Based Test Improves Endoscopic Ultrasound–Guided Cytologic Diagnosis of Pancreatic Cancer

Clinical Gastroenterology and Hepatology (2014)

Randall E. Brand Alex Adai Barbara A. Centeno Linda Lee George Rateb

Cytopathology

Endoscopic Ultrasound

10.1016/j.cgh.2014.02.038

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Citations (34)

MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma

Oncogene (2007)

Anna E. Szafranska Timothy S. Davison J. John Timothy Lewis Cannon Bence Sipos

Ductal cells

10.1038/sj.onc.1210228

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Citations (663)

Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factor

Nucleic Acids Research (1998)

Emmanuel Labourier Ferdinando Rossi Imed‐Eddine Gallouzi Eric Allemand Gilles Divita

Human DNA topoisomerase I, known for its DNA-relaxing activity, is possibly one of the kinases phosphorylating members of the SR protein family of splicing factors, in vivo. Little is known about the mechanism of action of this novel kinase. Using the prototypical SR protein SF2/ASF (SRp30a) as model substrate, we demonstrate that serine residues phosphorylated by topo I/kinase exclusively located within the most extended arginine-serine repeats of the SF2/ASF RS domain. Unlike other kinases such as cdc2 and SRPK1, which also phosphorylated serines at the RS domain, topo I/kinase required several SR dipeptide repeats. These repeats possibly contribute to a versatile structure in the RS domain thereby facilitating phosphorylation. Furthermore, far-western, fluorescence spectroscopy and kinase assays using the SF2/ASF mutants, demonstrated that kinase activity and binding were tightly coupled. Since the deletion of N-terminal 174 amino acids of Topo I destroys SF2/ASF binding and kinase activity but not ATP binding, we conclude that at least two distinct domains of Topo I are necessary for kinase activity: one in the C-terminal region contributing to the ATP binding site and the other one in the N-terminal region that allows binding of SF2/ASF.

SR protein

Protein kinase domain

MAP2K7

10.1093/nar/26.12.2955

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Citations (88)

Establishment and Validation of Analytical Reference Panels for the Standardization of Quantitative BCR-ABL1 Measurements on the International Scale

Clinical Chemistry (2013)

Helen White John Hedges Israel Bendit Susan Branford Dolors Colomer

BACKGROUND Current guidelines for managing Philadelphia-positive chronic myeloid leukemia include monitoring the expression of the BCR-ABL1 (breakpoint cluster region/c-abl oncogene 1, non-receptor tyrosine kinase) fusion gene by quantitative reverse-transcription PCR (RT-qPCR). Our goal was to establish and validate reference panels to mitigate the interlaboratory imprecision of quantitative BCR-ABL1 measurements and to facilitate global standardization on the international scale (IS). METHODS Four-level secondary reference panels were manufactured under controlled and validated processes with synthetic Armored RNA Quant molecules (Asuragen) calibrated to reference standards from the WHO and the NIST. Performance was evaluated in IS reference laboratories and with non–IS-standardized RT-qPCR methods. RESULTS For most methods, percent ratios for BCR-ABL1 e13a2 and e14a2 relative to ABL1 or BCR were robust at 4 different levels and linear over 3 logarithms, from 10% to 0.01% on the IS. The intraassay and interassay imprecision was <2-fold overall. Performance was stable across 3 consecutive lots, in multiple laboratories, and over a period of 18 months to date. International field trials demonstrated the commutability of the reagents and their accurate alignment to the IS within the intra- and interlaboratory imprecision of IS-standardized methods. CONCLUSIONS The synthetic calibrator panels are robust, reproducibly manufactured, analytically calibrated to the WHO primary standards, and compatible with most BCR-ABL1 RT-qPCR assay designs. The broad availability of secondary reference reagents will further facilitate interlaboratory comparative studies and independent quality assessment programs, which are of paramount importance for worldwide standardization of BCR-ABL1 monitoring results and the optimization of current and new therapeutic approaches for chronic myeloid leukemia.

ABL

breakpoint cluster region

Certified reference materials

10.1373/clinchem.2012.196477

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Citations (50)