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| Item Type: | Article |
|---|---|
| Title: | m(6)A-mRNA methylation regulates cardiac gene expression and cellular growth |
| Creators Name: | Kmietczyk, V. and Riechert, E. and Kalinski, L. and Boileau, E. and Malovrh, E. and Malone, B. and Gorska, A. and Hofmann, C. and Varma, E. and Jürgensen, L. and Kamuf-Schenk, V. and Altmüller, J. and Tappu, R. and Busch, M. and Most, P. and Katus, H.A. and Dieterich, C. and Völkers, M. |
| Abstract: | 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 N(6)-position (m(6)A). 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 m(6)A in human and murine-dilated cardiac tissue remains unknown. Transcriptome-wide mapping of m(6)A in mRNA allowed us to catalog m(6)A vtargets in human and murine hearts. Increased m(6)A methylation was found in human cardiomyopathy. Knockdown and overexpression of the m(6)A 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 m(6)A sites could be a powerful approach to prevent worsening of cardiac function. |
| Keywords: | Adenosine, Cardiac Myocytes, Cell Enlargement, Cell Proliferation, Cell Size, Cohort Studies, Cultured Cells, Dilated Cardiomyopathy, Gene Expression Regulation, Gene Knockdown Techniques, Messenger RNA, Methylation, Methyltransferases, Protein Biosynthesis, Animals, Mice, Rats |
| Source: | Life Science Alliance |
| ISSN: | 2575-1077 |
| Publisher: | Life Science Alliance |
| Volume: | 2 |
| Number: | 2 |
| Page Range: | e201800233 |
| Date: | April 2019 |
| Official Publication: | https://doi.org/10.26508/lsa.201800233 |
| PubMed: | View item in PubMed |
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