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Cross-evolutionary dissection of the functional plasticity of the ribosomal epitranscriptome

Descrizione del progetto

Svelare il ruolo funzionale delle modifiche dell’RNA ribosomale

L’RNA ribosomale (rRNA) è un componente integrante dei ribosomi, in cui ha luogo la sintesi proteica. Prove emerse indicano l’esistenza di modifiche epigenetiche dell’rRNA che variano in cellule diverse o in condizioni ambientali diverse. Ciò suggerisce che la regolazione delle proprietà del ribosoma possa avere luogo tramite modifiche dell’rRNA e rifletterne l’adattamento a un nuovo ambiente, uno stress specifico o uno stato patologico. L’obiettivo principale del progetto EpiRibo, finanziato dall’UE, è quello di profilare le modifiche dell’rRNA in diversi tipi di cellule e fare luce sulla loro regolazione tramite l’evoluzione. Inoltre, tramite approcci con acquisto o perdita di funzione, gli scienziati sveleranno le funzioni dei ribosomi derivanti dalle modifiche dell’RNA.

Obiettivo

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.

Campo scientifico

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.

Meccanismo di finanziamento

ERC-COG - Consolidator Grant

Istituzione ospitante

WEIZMANN INSTITUTE OF SCIENCE
Contribution nette de l'UE
€ 2 000 000,00
Indirizzo
HERZL STREET 234
7610001 Rehovot
Israele

Mostra sulla mappa

Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 2 000 000,00

Beneficiari (1)