Download Exporter la page en pdf

Team Publications
RNA Biology linked to DNA damage
Year of publication 2010
Tony Durand, Gaëtana Di Liberto, Hélène Colman, Anne Cammas, Sebastien Boni, Patrick
Marcellin, Annie Cahour, Stephan Vagner, Cyrille Féray (2010 Jul 1)
Occult infection of peripheral B cells by hepatitis C variants which have low
translational efficiency in cultured hepatocytes.
Gut : 934-42 : DOI : 10.1136/gut.2009.192088
Summary
Plasma hepatitis C virus (HCV) originates from hepatocytes. However, in certain subjects, B
cells may harbour both plasma strains and occult HCV strains tha t are not detected in the
plasma. The internal ribosome entry site (IRES) of these latter strains is mutated, suggesting
that the efficiency of viral translation could drive the cellular tropism of HCV.
Stefania Millevoi, Stéphan Vagner (2010 May 1)
Molecular mechanisms of eukaryotic pre-mRNA 3′ end processing regulation.
Nucleic acids research : 2757-74 : DOI : 10.1093/nar/gkp1176
Summary
Messenger RNA (mRNA) 3′ end formation is a nuclear process through which all eukaryotic
primary transcripts are endonucleolytically cleaved and most of them acquire a poly(A) tail.
This process, which consists in the recognition of defined poly(A) signals of the pre-mRNAs
by a large cleavage/polyadenylation machinery, plays a critical role in gene expression.
Indeed, the poly(A) tail of a mature mRNA is essential for its functions, including stability,
translocation to the cytoplasm and translation. In addition, this process serves as a bridge in
the network connecting the different transcription, capping, splicing and export machineries.
It also participates in the quantitative and qualitative regulation of gene expression in a
variety of biological processes through the selection of single or alternative poly(A) signals in
transcription units. A large number of protein factors associates with this machinery to
regulate the efficiency and specificity of this process and to mediate its interaction with
other nuclear events. Here, we review the eukaryotic 3′ end processing machineries as well
as the comprehensive set of regulatory factors and discuss the different molecular
mechanisms of 3′ end processing regulation by proposing several overlapping models of
regulation.
Martin Dutertre, Magali Lacroix-Triki, Keltouma Driouch, Pierre de la Grange, Lise Gratadou,
Samantha Beck, Stefania Millevoi, Jamal Tazi, Rosette Lidereau, Stephan Vagner, Didier Auboeuf
(2010 Feb 1)
Exon-based clustering of murine breast tumor transcriptomes reveals
alternative exons whose expression is associated with metastasis.
Cancer research : 896-905 : DOI : 10.1158/0008-5472.CAN-09-2703
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1
Team Publications
RNA Biology linked to DNA damage
Summary
In the field of bioinformatics, exon profiling is a developing area of disease-associated
transcriptome analysis. In this study, we performed a microarray-based transcriptome
analysis at the single exon level in mouse 4T1 primary mammary tumors with different
metastatic capabilities. A novel bioinformatics platform was developed that identified 679
genes with differentially expressed exons in 4T1 tumors, many of which were involved in cell
morphology and movement. Of 152 alternative exons tested by reverse transcription-PCR,
97 were validated as differentially expressed in primary tumors with different metastatic
capability. This analysis revealed candidate progression genes, hinting at variations in
protein functions by alternate exon usage. In a parallel effort, we developed a novel exonbased clustering analysis and identified alternative exons in tumor transcriptomes that were
associated with dissemination of primary tumor cells to sites of pulmonary metastasis. This
analysis also revealed that the splicing events identified by comparing primary tumors were
not aberrant events. Lastly, we found that a subset of differentially spliced variant transcripts
identified in the murine model was associated with poor prognosis in a large clinical cohort of
patients with breast cancer. Our findings illustrate the utility of exon profiling to define novel
theranostic markers for study in cancer progression and metastasis.
Year of publication 2009
Gérard Maillot, Magali Lacroix-Triki, Sandra Pierredon, Lise Gratadou, Sabine Schmidt, Vladimir
Bénès, Henri Roché, Florence Dalenc, Didier Auboeuf, Stefania Millevoi, Stéphan Vagner (2009
Nov 1)
Widespread estrogen-dependent repression of micrornas involved in breast
tumor cell growth.
Cancer research : 8332-40 : DOI : 10.1158/0008-5472.CAN-09-2206
Summary
Altered expression of microRNAs (miRNA), an abundant class of small nonprotein-coding
RNAs that mostly function as negative regulators of protein-coding gene expression, is
common in cancer. Here, we analyze the regulation of miRNA expression in response to
estrogen, a steroid hormone that is involved in the development and progression of breast
carcinomas and that is acting via the estrogen receptors (ER) transcription factors. We set
out to thoroughly describe miRNA expression, by using miRNA microarrays and real-time
reverse transcription-PCR (RT-PCR) experiments, in various breast tumor cell lines in which
estrogen signaling has been induced by 17beta-estradiol (E(2)). We show that the expression
of a broad set of miRNAs decreases following E(2) treatment in an ER-dependent manner.
We further show that enforced expression of several of the repressed miRNAs reduces E(2)dependent cell growth, thus linking expression of specific miRNAs with estrogen-dependent
cellular response. In addition, a transcriptome analysis revealed that the E(2)-repressed
miR-26a and miR-181a regulate many genes associated with cell growth and proliferation,
including the progesterone receptor gene, a key actor in estrogen signaling. Strikingly,
miRNA expression is also regulated in breast cancers of women who had received
antiestrogen neoadjuvant therapy. Overall, our data indicate that the extensive alterations in
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 2
Team Publications
RNA Biology linked to DNA damage
miRNA regulation upon estrogen signaling pathway play a key role in estrogen-dependent
functions and highlight the utility of considering miRNA expression in the understanding of
antiestrogen resistance of breast cancer.
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 3