RNA EDITING IN HEALTH AND DISEASE

Informazioni relative al progetto

RNAEDIT

ID dell’accordo di sovvenzione: 649019

DOI

10.3030/649019

Progetto chiuso

Data della firma CE 1 Ottobre 2015

Data di avvio 1 Gennaio 2016

Data di completamento 31 Dicembre 2021

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 2 270 000,00

Contributo UE

€ 2 270 000,00

Coordinato da

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany

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

Periodo di rendicontazione: 2020-12-01 al 2021-12-31

Sintesi del contesto e degli obiettivi generali del progetto

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).

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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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