Cosmin Saveanu

Education

Medical Degree (1996), Cluj, Romania – scientific report on a method for multiple substrate enzyme kinetics parameter estimation. PhD in biochemistry (2001) supervised by Mircea Cucuianu, Cluj, Romania, on the characterisation of proteins through complex purification and mass-spectrometry identification. Habilitation for PhD supervising, HDR (2010) Paris Diderot University (now part of Université Paris Cité).

Honors

Silver medal at the 22nd International Chemistry Olympiad (1990), Thérèse Lebrasseur prize (2019)

Past achievements

(PubMed publications or Google Scholar citations. All my publications or author manuscripts are on HAL-Pasteur)

Deadenylation and its relative importance for mRNA degradation

The textbook version of RNA degradation mechanisms describes deadenylation as the limiting step in the process. Previous publications and our own results (EMBOJ, 2024) tend to demonstrate that this texbook view is far from the reality of the complex processes involved in mRNA degradation. We used cutting edge methods of gene inactivation (inducible degron), RNA sequencing (Nanopore) and mRNA dynamics analysis (metabolic labeling and chase) to show that it is rather the rated of decapping that is limiting in yeast mRNA degradation and that even when deadenylation is slowed down, reporter and endogenous mRNA maintain their stabilities.

Translation-dependent mRNA degradation in yeast involves unexplored mechanisms and substrates

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 systematic analysis of NMD complexes and discovered two mutually exclusive macromolecular assemblies required for this degradation pathway (EMBOJ, 2018). The study of how these assemblies form and how their activity is regulated led to new collaborative results (e.g., PLoS Biol, 2024). The main project on NMD and RNA degradation pathways was 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“.

Genetic interaction profiles are excellent predictors of gene function

In search for new ways to explore gene function, I participated to the development of a method that allows to measure on a large scale the impact on growth of introducing mutants of two different genes in the same strain (Genetic Interactions Mapping, GIM). The best predictor for an unknown gene function can be found by correlating the profiles of sensitivity of mutants to a range of perturbations (PNAS, 2008). A larger scale genome-wide set of screens that I coordinated, led to results that identified new genes involved in RNA transport, maturation and degradation (Nucleic Acids Res, 2021) and triggered several collaborative publications (e.g. Nature Comm 2021, Antimicrob Agents Chemother 2016, Nucleic Acids Res 2014,  PNAS 2013).

Funded by young investigator ANR-08-JCJC0019-01, GENO-GIM (2008-2012)