Présentation

Regulation of RNA stability and translation are two key steps of cellular homeostasis. For a long time these posttranscriptional processes were considered as intermediary minor steps of gene expression. However recent works clearly demonstrate that RNA stability per-se is critical for cell homeostasis. Similarly, the translatability of an mRNA is a bottleneck in the control chain of gene expression and has been shown to be an efficient checkpoint. In line with this, our team focuses its activities on understanding and deciphering specific pathways controlling RNA stability as well as the translation process and the consequences of their dysfunction in different pathologies. In the past, we have been working on two cellular factors, the translation initiation factor INT6/EIF3E and the RNA helicase UPF1, that act at the crossroads of RNA translation and decay. The pleiotropic effects of both proteins are perfect examples of the im​portance of RNA decay and translation in maintaining correct cell functioning. It also illustrates the evident coordination between both processes as well as the high complexity of their links.

Infection by the oncovirus HTLV-1 constitutes a useful model to address those issues. We established recently how the viral protein Tax is able to interact and alter some functions of INT6/EIF3E and UPF1, especially in Nonsense Mediated mRNA Decay (NMD). This leads us to study the consequences of UPF1 inhibition by HTLV-1 and evaluate its impact on the associated pathologies (project 1).

To better apprehend how a RNA can act on gene expression regulation as part of a RiboNucleoProtein complex (RNP), we are also interested in specific RNP formations and processings. In addition to the RNA helicase UPF1, we develop an axis of research based on the G4 resolvase DHX36 (project 2).

Regulation of mRNA translation is another important aspect of the posttranscriptional control of gene expression. In this regard, we plan to further address the role of INT6/EIF3E in the regulation of mRNA translation and how this function impacts genetic instability and cancer development (project 3 and 4).

Our studies are carried out with various biochemichal, molecular and cellular approaches including highthroughput analyses and a model of humanized mice.