The group "Expression of eukaryotic mRNAs" was created in 2009 with support from the ATIP program of the CNRS in the « Functional Genomic » section of IBENS (Institut de Biologie de l’Ecole Normale Supérieure).
Our research projects are funded by "ANR", "Ligue contre le cancer" and "Fondation pour la Recherche Médicale" (as « Equipe FRM 2010 »).
In eukaryotic cells, genetic information is carried by messenger RNAs (mRNA) that exist as ribonucleoprotein particules (mRNP). Our laboratory studies the assembly of mRNP particules because their composition and their structure are extremely dynamic and are the targets of various gene expression regulatory inputs via RNA binding proteins and small RNAs (Moore & Proudfoot, 2009). More precisely, we focus our attention on the Exon Junction Complex (EJC, Le Hir et al. 2000), a multiprotein complex deposited on mRNA as a consequence of splicing.
EJCs accompany mRNAs to the cytoplasm and during this travel, they communicate with several cellular machineries to modulate mRNA transport, translation and quality control.
Our group combines different experimental approaches including biochemistry, molecular and cellular biology to determine the assembly pathway and the mode of action of the EJC.
With purified recombinant proteins, we try to reconstitute different forms of the complex. This strategy allowed us to elucidate the original mean by which the EJC core binds RNA (Ballut et al. 2005) and to show that the EJC core serves as a platform to recruit and regulate additional proteins involved in mRNA metabolism (Chamieh et al. 2008 ; Buchwald et al. 2010). The reconstituted complexes are also subjected to cristallographic analyses in collaboration with structural biologists (Andersen et al. 2006 ; Nielsen et al. 2009 ; Buchwald et al. 2010).
In addition, we study EJC assembly in vivo in different cultured cell lines, which led us to the finding that the EJC is not a constitutive mark of splicing but instead is loaded on particular mRNAs and on specific exon junctions (Saulière et al. 2010).
Today, the main objective of the laboratory is to find out - by a combination of methods developed in vitro and in vivo - the factors that regulate EJC deposition and to determine the impact of EJC on mRNA expression and quality control in different cellular environments.
- Andersen et al. (2006). Science 313:1968-1972.
- Ballut et al. (2005). Nature Structural and Molecular Biology 12(10):861-9.
- Buchwald et al. (2010). P.N.A.S. 107(22):10050–10055.
- Chamieh et al. (2008). Nature Structural and Molecular Biology. 15(1):85-93.
- Le Hir H et al. (2000). EMBO 19(24):6860-6869.
- Moore & Proudfoot (2009). Cell 136:688–700.
- Nielsen et al. (2009). RNA 15:1-9.
- Saulière et al. (2010). Nature Structural and Molecular Biology. 17(10):1269-71.

