ERC Starting Grant · 2024
Dissecting transcription termination and RNA sorting in MYCN-driven tumors
The inherent stresses arising from oncogenic transcription can be counteracted by premature termination which removes RNA polymerase II (RNAPII) from DNA and enables the degradation of aberrant nascent RNA by the nuclear exosome. When overexpressed, the MYCN oncoprotein fuels the growth of aggressive tumors by globally binding active promoters and invariably enhancing RNAPII transcription. However, I have made two key discoveries showing that the function of MYCN is not restricted to gene activation: Firstly, MYCN interacts with the exosome and prevents conflicts of RNAPII with replication forks to avert lethal DNA damage. Secondly, MYCN globally leaves promoters and directly binds nascent…
From the public funding record at EU CORDIS. Describes the funded project, not the reviews below.