Decoding the targets of CVD-relevant lncRNAs and genetically deciphering their mechanisms of action in vivo (B10*)

• Subject Area: Human Genetics
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 403584255

The Firre locus produces a conserved trans-acting lncRNA involved in multiple biological processes; nevertheless, the role of Firre for heart function has not been addressed. Our transcriptomic and initial phenotypic analysis in Firre loss-of-function mutants point to a functional role in the heart. We will perform loss- and gain-of-function experiments and perform an extensive transcriptomic and phenotypic analysis post-myocardial infarction (MI) to resolve the role of Firre in cardiovascular disease (CVD). To gain mechanistic insights into how Firre controls its target genes, we will evaluate triplex-forming potential nearby the disease-specific Firre targets. Finally, we will use our developed Allelome.LINK approach to identify additional CVD-relevant lncRNAs. This strategy takes advantage of the allele-specific information to link lncRNAs to their putative target genes and predicts their mode of action, bringing us closer to understanding the impact of the non-coding genome on heart disease.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 267: Non-coding RNA in the cardiovascular system
• Applicant Institution: Technische Universität München (TUM)
• Project Head: Dr. Daniel Andergassen