Long non-coding RNAs
General scientific objectives:
The majority of the human genome comprises non-coding sequences, which include long non-coding RNAs (lncRNAs). Discriminated by their length of more than 200 nucleotides, lncRNAs are involved in complex biological processes, executed by a multitude of mechanisms: Whereas for some non-coding RNAs the RNA structure itself already provides functionality, others operate in RNA-protein-complexes. Consequently, their functional spread ranges from RNA catalysis over gene regulation and scaffolding to recruitment of chromatin modifying enzymes. First studies of our Institute suggest that lncRNAs and non-coding circular RNAs, which are generated by back-splicing, play critical roles in the cardiovascular system (Michalik et al., 20141; Boeckel et al., 20152; Boon et al, 20163; Neumann, Jaé et al., 20184). Recently, the lncRNA GATA6-AS was shown to regulate endothelial gene expression by association with the chromatin modifier LOXL2 (Neumann, Jaé et al., 20184). In addition we identified several hypoxia or disease-regulated lncRNAs and circRNAs, which are currently explored with respect to their function and molecular mechanism.
Molecular mechanisms of hypoxia-controlled lncRNAs: Dr. Nicolas Jaé (Group leader), Youssef Fouani, Luisa Kirchhof, Andrea Knau
LncRNAs in cardiovascular disease: Dr. Alisha Haug, Jessica Neitz, Marie-Christine Hartmann
circRNAs: Andreas Heumüller, Marius Klangwart
- Michalik KM, You X, Manavski Y, et al. Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth. Circ Res. 2014;114(9):1389-1397.
- Boeckel J-N, Jaé N, Heumüller AW, et al. Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA. Circ Res. 2015;117(10):884-890.
- Boon RA, Jaé N, Holdt L, Dimmeler S. Long Noncoding RNAs. J Am Coll Cardiol. 2016;67(10):1214-1226.
- Neumann P, Jaé N, Knau A, et al. The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2. Nat Commun. 2018;9(1):237.