Fate determination of nuclear polyadenylated RNA
Name of applicant
Torben Heick Jensen
Title
Professor
Institution
Aarhus University
Amount
DKK 24,998,116
Year
2024
Type of grant
Semper Ardens: Advance
What?
Mammalian genomes generate transcripts from as much as 80-90% of their DNA, yet functional RNAs only constitute ~3% of genomic space. Since the majority of the remaining RNA is turned over in the cell nucleus, efficient quality control is urgently required. The project will delineate which molecular features and mechanisms sort RNA for nuclear export vs. degradation.
Why?
Proper maintenance and differentiation of cells rely on tight control of RNA homeostasis. Therefore, it is central for cells to sort functional from non-functional transcripts, which is underscored by the fact that mutation of RNA turnover complexes are strongly linked to disease. How such sorting takes place at the molecular level is not known.
How?
We will conduct state-of-the-art high throughput analysis of nuclear RNA export/turnover to determine involved RNA elements. Moreover, we will employ in vivo protein-protein interaction technologies to identify related factors and uitilize these in kinetic RNA-protein interaction profiling in cells to establish critical commitment steps, dictating fate determination of nuclear polyadenylated RNA.