I coordinated the generation of a collection of 900 yeast strains in which a long 3′ untranslated region (UTR) replaced the normal UTR, in an attempt to destabilize the mRNA. Initially to be used as a tool to systematically explore the function of essential genes, the collection turned out to be valuable to identify the importance of the translated region length in mRNA stability (Cell Rep
, 2014). Work in collaboration with my colleagues showed that the involved degradation mechanism, called NMD
, for nonsense-mediated mRNA decay, affects a massive number of transcripts, generated from about half of yeast genes. These abortive transcripts result from an intrinsic inability of RNA polymerase II to precisely start transcription (eLife, 2015). How exactly NMD substrates are degraded cannot be discovered without highly sensitive biochemical assays. We performed a large number of systematic analyses of NMD complexes and discovered two mutually exclusive macromolecular assemblies required for this degradation pathway (EMBOJ, 2018). How these assemblies form and how their activity is regulated are currently under investigation.
The main project on NMD and RNA degradation pathways funded through ANR:
CleaNMD, ANR-14-CE10-0014, 2014-2018, and DEFineNMD, ANR-18-CE11-0003, 2019-2023. We benefit from support from the French Ministry of higher education, research and innovation
and from the “Fondation ARC pour la recherche sur le cancer
“. Our laboratory is affiliated to the “Complexité du Vivant” doctoral school
, Sorbonne University.