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

Project description

Unveiling the functional role of ribosomal RNA modifications

Ribosomal RNA (rRNA) is an integral component of ribosomes where protein synthesis takes place. Emerging evidence indicates the existence of epigenetic modifications on rRNA which vary in different cells or under different environmental conditions. This suggests that the regulation of ribosome properties may take place through rRNA modifications and reflect adaptation to a new environment, stress or a pathological state. The key objective of the EU-funded EpiRibo project is to profile rRNA modifications in different cell types and shed light on their regulation through evolution. Moreover, through gain- and loss-of-function approaches, scientists will unveil the functions of ribosomes resulting from RNA modifications.

Objective

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.

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Coordinator

WEIZMANN INSTITUTE OF SCIENCE
Net EU contribution
€ 2 000 000,00
Address
Herzl street 234
7610001 Rehovot
Israel

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Activity type
Higher or Secondary Education Establishments
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Other funding
€ 0,00

Beneficiaries (1)