A-to-I RNA editing of Filamin A regulates cellular adhesion, migration and mechanical properties.
Mamta JainAndreas WeberKathrin MalyGreeshma ManjalyJoanna DeekOlena TsvyetkovaMaja StulićJosé L Toca-HerreraMichael F JantschPublished in: The FEBS journal (2022)
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.
Keyphrases
- cell migration
- crispr cas
- smooth muscle
- induced apoptosis
- amino acid
- nucleic acid
- healthcare
- transcription factor
- endothelial cells
- public health
- cell cycle arrest
- bone marrow
- signaling pathway
- oxidative stress
- binding protein
- cell proliferation
- heat stress
- cell therapy
- health information
- biofilm formation
- atomic force microscopy
- high resolution
- extracellular matrix
- social media