RNA EDITING IN HEALTH AND DISEASE

Informations projet

RNAEDIT

N° de convention de subvention: 649019

DOI

10.3030/649019

Projet clôturé

Date de signature de la CE 1 Octobre 2015

Date de début 1 Janvier 2016

Date de fin 31 Decembre 2021

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 270 000,00

Contribution de l’UE

€ 2 270 000,00

Coordonné par

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany

Periodic Reporting for period 5 - RNAEDIT (RNA EDITING IN HEALTH AND DISEASE)

Période du rapport: 2020-12-01 au 2021-12-31

Résumé du contexte et des objectifs généraux du projet

The main objectives are to
(a) catalog RNA editing events in the context of tumour progression and then most importantly to
(b) understand the relevance of such events to tumour development and maintenance.
Given the emerging understanding of the importance of RNA editing to disease progression and manifestations, these findings will be of fundamental importance to our understanding of diseases that are heritable but lack a clear genetic component (and by extension, to novel therapeutic approaches to countering them).

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

To date, we have profiled ~110 DLBCL tumours at the RNA level but also through whole genome sequencing, and have identified through comparisons between RNA and DNA, thousands of editing events that are common to individual tumours. We have validated many of these, and are now attempting to address the impact of editing on individual pathways within the cells of interest.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

We have identified editing events common to individual tumours that are known to arise as mutations at the population level upon DLBCL relapse. This finding raises the distinct possibility that RNA editing (which is co-transcriptional) pre-dates DNA mutation and that the editing enzymes themselves (which are known to also target DNA albeit at lower frequencies) might be upregulated for RNA targeting purposes in the context of inflammation and tumour progression but might also become the direct catalysts for DNA mutation. This result, which we are now trying to validate, was unexpected but is of fundamental importance to cancer genesis.

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