Research topic 2: Investigation of transcriptional elongation

While the target genes of MYC have been extensively analyzed by other research groups and us in recent years, the actual mechanism by which MYC regulates target genes was unclear. It was also unclear whether MYC fundamentally alters the transcriptional process of cells, as seems possible considering the global binding behavior of MYC. In order to investigate how and why MYC alters the transcription machinery globally, my research group has set up two experimental systems: we both carried out a series of mass spectrometric investigations with MYC and the RNA polymerase and analyzed the global transcriptional behavior (4sU-sequencing, ChIP-sequencing).

These data result in the surprising and consequential model that, contrary to expectations, MYC does not primarily change the initiation (=transcription rate), but instead loads the RNA polymerase with elongation factors. If this loading mechanism is absent when MYC is inactivated, the RNA polymerase loses a great deal of its processing power. Therefore, the inactivation of MYC leads to the production of abortive, non-protein-coding transcripts instead of intact mRNAs (Baluapuri et al, Molecular Cell, 2019). This observation raises the question of what the biological role of this abortive transcription is.