Fendrr synergizes with Wnt signalling to regulate fibrosis related genes during lung development via its RNA:dsDNA triplex element

Author:

Ali Tamer123,Rogala Sandra13,Krause Nina M4,Bains Jasleen Kaur4,Melissari Maria-Theodora1,Währisch Sandra5,Schwalbe Harald4ORCID,Herrmann Bernhard G5,Grote Phillip13ORCID

Affiliation:

1. Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University , Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Hesse , Germany

2. Faculty of Science, Benha University , Benha 13518 , Egypt

3. Georg-Speyer-Haus , Paul-Ehrlich-Str. 42-44, 60596 Frankfurt am Main, Hesse , Germany

4. Center for Biomolecular Magnetic Resonance (BMRZ), Institute for Organic Chemistry and Chemical Biology, Goethe University , Max-von-Laue-Str. 7, 60438 , Frankfurt am Main, Hesse , Germany

5. Department of Developmental Genetics, Max Planck Institute for Molecular Genetics , Ihnestr. 63-73, 14195 Berlin , Germany

Abstract

Abstract Long non-coding RNAs are a very versatile class of molecules that can have important roles in regulating a cells function, including regulating other genes on the transcriptional level. One of these mechanisms is that RNA can directly interact with DNA thereby recruiting additional components such as proteins to these sites via an RNA:dsDNA triplex formation. We genetically deleted the triplex forming sequence (FendrrBox) from the lncRNA Fendrr in mice and found that this FendrrBox is partially required for Fendrr function in vivo. We found that the loss of the triplex forming site in developing lungs causes a dysregulation of gene programs associated with lung fibrosis. A set of these genes contain a triplex site directly at their promoter and are expressed in lung fibroblasts. We biophysically confirmed the formation of an RNA:dsDNA triplex with target promoters in vitro. We found that Fendrr with the Wnt signalling pathway regulates these genes, implicating that Fendrr synergizes with Wnt signalling in lung fibrosis.

Funder

DFG

Max-Planck-Gesellschaft

Publisher

Oxford University Press (OUP)

Subject

Genetics

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