RNA EDITING IN HEALTH AND DISEASE

Projektinformationen

RNAEDIT

ID Finanzhilfevereinbarung: 649019

DOI

10.3030/649019

Projekt abgeschlossen

EK-Unterschriftsdatum 1 Oktober 2015

Startdatum 1 Januar 2016

Enddatum 31 Dezember 2021

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 2 270 000,00

EU-Beitrag

€ 2 270 000,00

Koordiniert durch

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany

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

Berichtszeitraum: 2020-12-01 bis 2021-12-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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).

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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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