PT  - JOURNAL ARTICLE
AU  - Kmietczyk, Vivien
AU  - Riechert, Eva
AU  - Kalinski, Laura
AU  - Boileau, Etienne
AU  - Malovrh, Ellen
AU  - Malone, Brandon
AU  - Gorska, Agnieszka
AU  - Hofmann, Christoph
AU  - Varma, Eshita
AU  - Jürgensen, Lonny
AU  - Kamuf-Schenk, Verena
AU  - Altmüller, Janine
AU  - Tappu, Rewati
AU  - Busch, Martin
AU  - Most, Patrick
AU  - Katus, Hugo A
AU  - Dieterich, Christoph
AU  - Völkers, Mirko
TI  - m<sup>6</sup>A-mRNA methylation regulates cardiac gene expression and cellular growth
AID  - 10.26508/lsa.201800233
DP  - 2019 Apr 01
TA  - Life Science Alliance
PG  - e201800233
VI  - 2
IP  - 2
4099  - http://www.life-science-alliance.org/content/2/2/e201800233.short
4100  - http://www.life-science-alliance.org/content/2/2/e201800233.full
SO  - Life Sci. Alliance2019 Apr 01; 2
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.