A‐to‐I RNA editing of Filamin A regulates cellular adhesion, migration and mechanical properties. (9th March 2022)

• Record Type: Journal Article
• Authors: Jain, Mamta; Weber, Andreas; Maly, Kathrin; Manjaly, Greeshma; Deek, Joanna; Tsvyetkova, Olena; Stulić, Maja; Toca‐Herrera, José L.; Jantsch, Michael F.
• Is Part Of: FEBS journal. Volume 289:Number 15(2022)
• Page Start: 4580
• Page End: 4601
• Publication Date: 2022-03-09
• Subjects: atomic force microscopy -- cell adhesion -- filamin A -- integrin signalling -- RNA editing; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.16391
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : A‐to‐I RNA editing by ADARs is an abundant epitranscriptomic RNA‐modification in metazoa. In mammals, Flna pre‐mRNA harbours a single conserved A‐to‐I RNA editing site that introduces a Q‐to‐R amino acid change in Ig repeat 22 of the encoded protein. Previously, we showed that FLNA editing regulates smooth muscle contraction in the cardiovascular system and affects cardiac health. The present study investigates how ADAR2‐mediated A‐to‐I RNA editing of Flna affects actin crosslinking, cell mechanics, cellular adhesion and cell migration. Cellular assays and AFM measurements demonstrate that the edited version of FLNA increases cellular stiffness and adhesion but impairs cell migration in both, mouse fibroblasts and human tumour cells. In vitro, edited FLNA leads to increased actin crosslinking, forming actin gels of higher stress resistance. Our study shows that Flna RNA editing is a novel regulator of cytoskeletal organisation, affecting the mechanical property and mechanotransduction of cells. Abstract : Herein, we investigated the impact of A‐to‐I RNA editing of filamin A on important cellular and mechanical processes. Flna pre‐mRNA harbours a single conserved A‐to‐I RNA editing site, leading to a Q‐to‐R amino acid exchange of the encoded protein. This study shows differential effects of FLNA hypo‐ (FLNA Q ) and hyper‐editing (FLNA R ) on cell stiffness, cell adhesion, cell migration and integrin internalization.