TY - JOUR T1 - m<sup>6</sup>A-mRNA methylation regulates cardiac gene expression and cellular growth JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800233 VL - 2 IS - 2 SP - e201800233 AU - Vivien Kmietczyk AU - Eva Riechert AU - Laura Kalinski AU - Etienne Boileau AU - Ellen Malovrh AU - Brandon Malone AU - Agnieszka Gorska AU - Christoph Hofmann AU - Eshita Varma AU - Lonny Jürgensen AU - Verena Kamuf-Schenk AU - Janine Altmüller AU - Rewati Tappu AU - Martin Busch AU - Patrick Most AU - Hugo A Katus AU - Christoph Dieterich AU - Mirko Völkers Y1 - 2019/04/01 UR - https://www.life-science-alliance.org/content/2/2/e201800233.abstract N2 - 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. ER -