Ubiquitin and Dynamics of Molecular Scaffolds
Program: Genomes and Epigenomes
Group Leader: Catherine DARGEMONT
Tel.: +33 (0)157278032dargemont.catherine@ijm.univ-paris-diderot.fr
Floor 3
Eukaryotic mRNA formation, as the result of gene expression, is submitted to a tight quality control. Transcripts generated by RNA polymerase II undergo a carefully orchestrated series of processing steps which involve the machineries responsible for chromatin modifications, transcription initiation, elongation and 3’ end maturation before being exported to the cytoplasm. The steps of mRNA biogenesis leading to export-competent ribonucleoprotein particles (mRNPs) are intimately coupled and coordinated by the RNA polymerase II (RNAPII) C-terminal domain (CTD), which acts as a recruitment platform for the different RNA processing machineries. Fully mature and correctly packaged yeast mRNPs are then released from the transcription site and transported into the cytoplasm by the export receptor Mex67, which promotes their translocation through the nuclear pore complexes.
Ubiquitin conjugation, capable of controlling both protein degradation but also protein/protein interactions, appears as a good candidate to favorize dynamic molecular scaffolds responsible for functional coupling events and in particular those responsible for mRNA biogenesis. Few years ago, we proposed that modifications by ubiquitin and their recognition by ubiquitin-binding domains could play a major role in the dynamic, assembly and coordination of the supramolecular scaffolds involved in transcription and mRNA nuclear export.
Major Research themes
We are mostly interested in the role of ubiquitin and ubiquitin binding domains
- in the dynamic of histone code and in particular in histone modifications associated with transcriptional activation such as H2B ubiquitylation and H3K4 methylation
- in coupling between 3’ end maturation (termination and polyadenylation) and nuclear export of mRNAs
- in coordinating transcription and targetting to the nuclear pore complex
- in regulating functions of the nuclear pore complex
In parallele, we participate, together with the Curie Institute biophotonic platform and team, to the application of high-resolution microscopy approaches for the study of nuclear substructures, such as the nuclear pore complex (Fig. 1).
Figure 1: Structure Illumination Microscopy (SIM) allows to distinguish nuclear and cytoplasmic nuclear pore proteins.
S. cerevisiae. nucleoporins : Nup60-GFP/Nup159-mcherry
Images Taken during "MIFOBIO 2010", Seignosses,France. Workshop n-SIM, Nikon
with PICT-IBiSA, Institut Curie (Paris) on samples provided by Babour A and Dargemont C. Jacques Monod Institute (Paris).
Copyright : Nikon/I. Curie/CNRS/IJM
Our team is labellised by the Ligue Nationale contre le Cancer since 2007
Sélection of Publications
H2B Ubiquitylation Controls the Formation of Export-Competent mRNP.
Vitaliano-Prunier A, Babour A, Hérissant L, Apponi L, Margaritis T, Holstege FC, Corbett AH, Gwizdek C, Dargemont C.
Mol Cell. 2012 Jan 13;45(1):132-9.
Abstract
Ubiquitylation of the nuclear pore complex controls nuclear migration during mitosis in S. cerevisiae.
Hayakawa A, Babour A, Sengmanivong L, Dargemont C.
J Cell Biol. 2012 Jan 9;196(1):19-27.
Abstract
Competition for XPO5 binding between Dicer mRNA, pre-miRNA and viral RNA regulates human Dicer levels.
Bennasser Y, Chable-Bessia C, Triboulet R, Gibbings D, Gwizdek C, Dargemont C, Kremer EJ, Voinnet O, Benkirane M.
Nat Struct Mol Biol. 2011 Mar;18(3):323-7.
Abstract
Ubiquitin-mediated mRNP dynamics and surveillance prior to budding yeast mRNA export.
Iglesias, N., Tutucci, E., Gwizdek, C., Vinciguerra, P., Von Dach E., Corbett, A., Dargemont, C. and Stutz, F.
Genes Dev. 2010 Sep 1;24(17):1927-38.
Abstract
Ubiquitylation of the COMPASS component Swd2 links H2B ubiquitylation to H3K4 trimethylation.
Vitaliano, A., Menant, A., Hobeika, M., Géli, V., Gwizdek, C. and Dargemont, C.
Nature Cell Biology 2008 Nov;10(11):1365-71.
Abstract
Last modified 01/23/2012