Missions

This study on mRNA quality control through translation in S. cerevisiae will involve molecular biology and biochemistry approaches dedicated to RNA and protein analysis (e.g., plasmid construction, northern and western blots, tagged protein constructs, protein fusions, immunoprecipitations), as well as yeast genetics (e.g., culture, selection, transformation, and construction of mutant strains via crossing, PCR, or CRISPR). Proteomics and RNA sequencing approaches will also be considered.

Activités

Messenger RNA (mRNA), a central element in the transmission of genetic information, constantly faces threats to its integrity due to various phenomena, such as transcription or RNA maturation defects, or from ribonucleolytic and chemical attacks that occur under conditions of stress, senescence, or neurodegenerative diseases. These defects lead to translation blockage, causing significant ribosome collisions which, once detected, trigger surveillance pathways such as No-Go Decay (NGD) and Non-Stop Decay (NSD). These pathways ensure the rapid degradation of defective mRNAs and the nascent peptides (referred to here as 'Arrest Peptides' or APs).

Remarkably, mRNA quality control, first described in yeast, is conserved across all eukaryotes studied so far. We will therefore continue the laboratory's ongoing research into the mechanisms activated when ribosomes are stalled within the coding sequence. It is proposed that these mRNAs are primarily degraded via 5' decapping followed by 5'-3' exonucleolytic degradation by the exoribonuclease Xrn1.

However, how the degradation of peptides (APs) and RNAs is coordinated remains poorly understood. Our current results support a model in which the decapping activator Pat1, conserved among eukaryotes, plays an important role in coordinating this ribosome-associated quality control. In the absence of this process, however, two potential endoribonucleases may act in a coupled manner, interfering with normal ribosome dissociation and affecting the canonical degradation of APs. Investigating the role of these two endoribonucleases as a backup system in these surveillance pathways is of particular interest.

Compétences

Strong practical knowledge in molecular biology and microbiology
Excellent understanding of yeast genetics
Solid experimental knowledge of RNA and protein biology
Attention to detail and rigor
Scientific curiosity, innovative mindset, and enthusiasm for experimental work
Autonomy and strong organizational skills
Ability to work in a team and contribute to collective projects
Good command of written and spoken English
Ability to use software tools for analyzing experimental data
Knowledge of and ability to apply hygiene and safety regulations

Contexte de travail

The position is based at the Institut de Biologie Physico-Chimique in Paris. The'Functional Regulation and RNA Surveillance team, in which the position is available, is part of the UMR8226 unit, the Laboratory of Molecular and Cellular Biology of Eukaryotes. The team consists of one researcher, two lecturer-researchers, one postdoctoral fellow, one PhD student, and two research assistants. The successful candidate will be under the supervision of the team leader.

Contraintes et risques

No particular constraints or risks.

Informations complémentaires

no comments