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

  • 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.

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Author:Tamer AliORCiD, Sandra RogalaGND, Nina M. Krause, Jasleen Kaur BainsORCiDGND, Maria-Theodora MelissariORCiD, Sandra Währisch, Harald SchwalbeORCiDGND, Bernhard HerrmannORCiDGND, Phillip GroteORCiD
URN:urn:nbn:de:hebis:30:3-856875
DOI:https://doi.org/10.1093/nar/gkad395
ISSN:0305-1048
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/37207329
Parent Title (English):Nucleic acids research
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Language:English
Date of Publication (online):2023/05/19
Date of first Publication:2023/05/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/05/24
Volume:51
Issue:12
Page Number:11
First Page:6227
Last Page:6237
HeBIS-PPN:521812984
Institutes:Medizin
Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International