Institut de recherches cliniques de Montréal
Our laboratory seeks to understand the biological functions of the intracellular localization of cellular RNA, essential molecules imlicated in all facets of gene expression that also serve to transmit genetic information for the synthesis of cellular proteins. For these studies, we use a combination of human and insect cell models, as well as an experimentally powerful model organism, the fruit fly Drosophila melanogaster. Combining the versatility of Drosophila genetics with high-throughput molecular imaging and functional genomics approaches, we aim to dissect the molecular mechanisms that control the targeting of different classes of cellular RNAs and their impact on cellular organization. Studies with simple model organisms, such as the fruit fly, have contributed greatly to our understanding of a variety of essential cellular processes and human diseases, including cancer.
Our projects aim to elucidate the normal functions of RNA traficking in the maintenance of cell polarity, as well as the regulation of genome stability and cell division. In addition, we have also initiated several projects that seek to understand how disruption of normal RNA localization pathways may contribute to the etiology of various human pathologies, including musculo-/neuro-degenerative diseases and cancer.
Finally, our laboratory is also actively collaborating within the ENCODE consortium (Encyclopedia of DNA Elements), an international group of experts in genomics and bioinformatics that seek to characterize regulatory elements (DNA and RNA) that modulate the expression of the Human genome. Specifically, we are participating withina team project led by Dr. Brenton Graveley (UConn) that aims to define the functions of 250 human RNA binding proteins (RBPs). In this context, our laboratory is performing i) high throughput imaging studies to characterize the intracellular distribution patterns of each RBP in different human cell lines, and ii) biochemical cellular fractionation combined with high-throughput RNA sequencing (RNA-Seq) to assess the functions of individual RBPs in subcellular RNA localization. These projects involve a broad combination of biochemical, genetic, molecular biology, and bioinformatics approaches.
- Iampietro, C., Bergalet, J., Wang, X., Cody, N.A., Chin, A., Lefebvre, F.A., Douziech, M., Krause, H.M., and Lécuyer, E. 2014. Developmentally-regulated elimination of damaged nuclei via a Chk2-dependent mechanism of mRNA nuclear retention. <http://www.ncbi.nlm.nih.gov/pubmed/24835465> Developmental Cell 29: 468-81.
- Cody, N.A., Iampietro, C., and Lécuyer, E. 2013. The many functions of mRNA localization during normal development and disease: from pillar to post.<http://www.ncbi.nlm.nih.gov/pubmed/24123937> WIREs Dev Biol 2:781-96.
- Zhang, Y,, Ponty, Y., Blanchette, M., Lécuyer, E., and Waldispühl, J. 2013. SPARCS: a web server to analyze (un)structured regions in coding RNA sequences.<http://www.ncbi.nlm.nih.gov/pubmed/23748952> Nucleic Acids Res 41(Web Server issue):W480-5.
- Wang, E.T., Cody, N.A., Jog, S., Biancollela, M., Wang, T.T., Treacy, D.J., Luo, S., Schroth, G.P., Housman, D.E., Reddy, S., Lécuyer, E., and Burge, C.B. 2012. Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins.<http://www.ncbi.nlm.nih.gov/pubmed/22901804> Cell 150:710-24.
- Lécuyer, E., Yoshida, H., Parthasarathy, N., Alm, C., Babak, T., Cerovina, T., Hughes, T.R., Tomancak, P., and Krause, H. M. 2007. Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function<http://www.ncbi.nlm.nih.gov/pubmed/17923096>. Cell 131, 174-87.