Résumés disponibles (92) :

GILLES Melissa (INSERM U1172 éq. 01 - Bruno LEFEBVRE)
Session :

 

@mail :  melissa.gilles@inserm.fr      tél. :  0651516151


Mots-clés : 

Titre de la communication :
A new role of Tau proteins in mRNA degradation by NMD pathway
Auteurs (et leurs adresses) de la communication :
Mélissa Gilles , Alban Chauderlier, Luc Buée , Marie-Christine Galas and Bruno Lefebvre. Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France
Résumé de la communication :
Tauopathies are neurodegenerative disorders characterized by the accumulation of aggregated Tau proteins. Tau proteins are mainly expressed in neurons and strongly localized in axons where they promote the assembly of microtubules. Recently, it has been shown that Tau displayed additional subcellular localizations suggesting this protein may have other functions than stabilizing microtubules. To gain some insights, we used a directed proteomic analysis of Tau-binding partners in cells using the tandem affinity purification (TAP)–mass spectrometry (MS) methodology. Our analysis identified the DEAD box RNA helicase DDX5 as a new partner. DDX5 is known to play a role in several RNA metabolic processes such as, splicing and NMD (nonsense-mediated mRNA decay) pathway. Our aims are to delineate the role of Tau/DDX5 interaction in normal physiology and its contribution to the pathogenesis of Tauopathies.

Tau/DDX5 interaction has been confirmed by co-immunoprecipitation, GST-pulldown and PLA (Proximity Ligation Assay) in SH-SY5Y cells. We also showed that Tau/DDX5 interaction is RNA-dependent and the presence of DDX5's known partner DDX17 in the complex. Using reporter system, we further demonstrated that Tau contributed to NMD and pre-mRNA splicing regulation in a DDX5 dependent manner.

Altogether, our results highlight a link between Tau and the DEAD box RNA helicase DDX5 and demonstrated an unexpected role of Tau in regulating NMD and pre-mRNA splicing. Our findings suggest that a loss of Tau functions may participate directly to the splicing and NMD target genes misregulation observed in Tauopathies.

GILLES Melissa (INSERM U1172 éq. 01 - Bruno LEFEBVRE)