Description du projet
Mettre en évidence le rôle fonctionnel des modifications de l’ARN ribosomal
L’ARN ribosomal (ARNr) est un élément essentiel des ribosomes, où se produit la synthèse des protéines. De nouvelles données mettent en évidence l’existence de modifications épigénétiques sur l’ARNr, qui varient en fonction des différentes cellules ou conditions ambiantes. Cela suggère que la régulation des propriétés des ribosomes peut se faire par le biais de modifications de l’ARNr et refléter l’adaptation à un nouvel environnement, au stress ou à un état pathologique. L’objectif principal du projet EpiRibo, financé par l’UE, consiste à établir le profil des modifications de l’ARNr dans différents types de cellules et à nous éclairer sur leur régulation au cours de l’évolution. Par ailleurs, grâce à des approches par gain et perte de fonction, les scientifiques parviendront à dévoiler les fonctions des ribosomes résultant des modifications de l’ARN.
Objectif
A remarkable diversity of post-transcriptional modifications adorn the ribosomal RNA (rRNA) throughout all domains of life. While initially conceptualized as a constitutive component of the ribosome, recent evidence demonstrates that some modifications are only present on a fraction of cellular ribosomes, and our lab recently revealed unprecedented environmentally-mediated dynamics of an rRNA modification. This suggests that some rRNA modification may serve as a tunable layer for regulation of ribosome properties, facilitating adaptation to a new environment, stress or pathological state. Here we aim to systematically explore the extent to which rRNA modifications are tunable across evolution and highly diverse growth conditions, and to understand the consequences thereof. We seek to understand which rRNA modifications are subject to regulation, to uncover the contexts in which such regulation occurs, and to unravel the underlying mechanisms. Dissecting these questions requires an approach allowing systematic measurement of diverse rRNA modifications. We propose to establish a streamlined workflow, allowing multiplexed, precise, robust and cost-efficient systematic profiling of 19 distinct rRNA modifications in dozens of samples in a single experiment (Aim 1). In Aim 2, we will systematically measure rRNA modifications across the three domains of life, focusing on species that can thrive across two widely different physical/chemical gradients, where the potential for tunable rRNA modifications is particularly high. In Aim 3, we will combine gain- and loss-of-function approaches to systematically explore the functions RNA modifications can bestow on ribosomes. Collectively, EpiRibo addresses a fundamental open question regarding the extent of plasticity and regulatory potential present within the ribosome itself and encoded via its epitranscriptome, setting the stage for investigations in other RNA species, and in more complex and disease-related contexts.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
7610001 Rehovot
Israël