Regulation of retinoic acid signaling by alternative polyadenylation

• Applicant: Professor Dr. Sven Danckwardt
• Subject Area: Hematology, Oncology ; Cell Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 470140790

Alternative polyadenylation (APA) is an evolutionarily conserved mechanism of posttranscriptional gene regulation. It affects more than 70% of all genes and thereby profoundly contributes to transcriptome 3’end diversification (TREND). In a large-scale RNAi screening, we recently discovered PCF11 as a pervasive component for proximal polyadenylation with a critical role in differentiation and dedifferentiation. However, the underlying mechanisms remained largely obscure. We now intend to explore how APA controls central signaling mechanisms involved in developmental programs. To this end, we will make use of bioinformatical, biochemical, and functional genomic approaches to disentangle the molecular and cellular effects of APA on retinoic acid (RA) signaling, a central pathway in embryonic development with a critical function in several pathophysiologies. Ultimately, these findings will be translated into an RA-dependent disease model (acute promyelocytic leukemia) to obtain first insights on the impact of this type of TREND regulation on progression, diagnosis and therapy of a human disease.

• DFG Programme: Research Grants