Molecular mechanisms of cardiovascular IncRNAs & RNA therapeutics

Non-coding RNAs (ncRNAs) are ribonucleic acid molecules that are not translated into proteins. Instead, they modulate complex molecular and cellular processes, for example gene expression, RNA maturation, and protein synthesis. In our team, we are interested in the molecular function of long non-coding RNAs (lncRNAs) and their implication in the cardiovascular system. Within the diverse class of non-coding RNAs, lncRNAsstand out by their board functional spread, ranging from RNA catalysis over gene regulation and scaffolding to recruitment of chromatin modifying enzymes. First studies of our Institute show that lncRNAs and covalently closed circular RNAs, which are generated by back-splicing, play critical roles in the cardiovascular system (Michalik et al., 2014; Boeckel et al., 2015; Jaé and Dimmeler 2020; Neumann and Jaé et al., 2018).

Our objective is the functional analysis of abundant lncRNAs in the light of cardiovascular development and disease, as well as the comprehensive characterization of novel, so far uncharacterized lncRNA candidates. In this regard, we identified the lncRNA GATA6-AS to regulate endothelial gene expression by association with the chromatin modifier LOXL2 (Neumann and Jaé et al., 2018) and are currently analyzing the role of lncRNAs in the hypoxic and shear-stress responses of endothelial cells. In addition, we elucidate the function of circular RNAs, which derive from back-splicing of linear RNAs. Here, we identified endothelial circRNAs (Boeckel et al, 2015) and are currently exploring their in vivo functions.      

Dr. Nicolas Jaé (Postdoc, Group leader)

Youssef Fouani (PhD student)

Luisa Kirchhof (PhD student)

Andreas Heumüller (PhD student)

Galip Aslan (PhD student)

Andrea Knau (Research assistant)

Circular RNAs 

Andreas Heumüller (PhD student)

Marius Klangwart (Research assistant) 

References:

1. 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

2. Jaé and Dimmeler. Noncoding RNAs in Vascular Diseases. Circ Res. 2020;126(9):1127-1145.

3. 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.

4. 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.