RT Journal Article SR Electronic T1 m6A-mRNA methylation regulates cardiac gene expression and cellular growth JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800233 DO 10.26508/lsa.201800233 VO 2 IS 2 A1 Vivien Kmietczyk A1 Eva Riechert A1 Laura Kalinski A1 Etienne Boileau A1 Ellen Malovrh A1 Brandon Malone A1 Agnieszka Gorska A1 Christoph Hofmann A1 Eshita Varma A1 Lonny Jürgensen A1 Verena Kamuf-Schenk A1 Janine Altmüller A1 Rewati Tappu A1 Martin Busch A1 Patrick Most A1 Hugo A Katus A1 Christoph Dieterich A1 Mirko Völkers YR 2019 UL https://www.life-science-alliance.org/content/2/2/e201800233.abstract AB Conceptually similar to modifications of DNA, mRNAs undergo chemical modifications, which can affect their activity, localization, and stability. The most prevalent internal modification in mRNA is the methylation of adenosine at the N6-position (m6A). This returns mRNA to a role as a central hub of information within the cell, serving as an information carrier, modifier, and attenuator for many biological processes. Still, the precise role of internal mRNA modifications such as m6A in human and murine-dilated cardiac tissue remains unknown. Transcriptome-wide mapping of m6A in mRNA allowed us to catalog m6A targets in human and murine hearts. Increased m6A methylation was found in human cardiomyopathy. Knockdown and overexpression of the m6A writer enzyme Mettl3 affected cell size and cellular remodeling both in vitro and in vivo. Our data suggest that mRNA methylation is highly dynamic in cardiomyocytes undergoing stress and that changes in the mRNA methylome regulate translational efficiency by affecting transcript stability. Once elucidated, manipulations of methylation of specific m6A sites could be a powerful approach to prevent worsening of cardiac function.