Localisation-dependent function of lncRNAs in cardiovascular disease: from mechanism to phenotype (A09*)

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

The timing of expression and localization of lncRNAs within the cell has a significant impact on their activity and genome regulation. We identified changes in intron retention (IR) levels coupled with a change in nuclear-cytoplasmic distribution of both mRNAs and lncRNAs in endothelial cells after hypoxia and in heart failure samples. These transcripts are mainly involved in the regulation of intracellular signaling pathways and helicase activity. In this project, we aim to understand the molecular mechanisms regulating IR and the role of IR-regulated nuclear-cytoplasmic localization changes of lncRNAs in regulating the response to hypoxia and in heart failure. We propose experiments using transcriptome-wide splicing analyses, RNA imaging, CRISPR, RNA-protein interaction analyses and massively parallel RNA assays. Overall, this project will shed light on the role of IR-driven subcellular localization changes of lncRNAs in cardiovascular diseases.

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