Author response: Mettl3-mediated m6A modification of Fgf16 restricts cardiomyocyte proliferation during heart regeneration

作者：Fu-Qing Jiang, Kun Liu, Jiaxuan Chen, Yan Cao, Wu-Yun Chen, Wan-Ling Zhao, Guohua Song, Chi-Qian Liang, Yi-Min Zhou, Huanlei Huang, Ruijin Huang, Hui Zhao, Kyu‐Sang Park, Zhenyu Ju, Dongqing Cai, Xufeng Qi · 年份：2022 · DOI：10.7554/elife.77014.sa2 · 研究领域：RNA modifications and cancer、Cardiac Structural Anomalies and Repair、Peptidase Inhibition and Analysis

Cardiovascular diseases are one of the world’s biggest killers. Even for patients who survive a heart attack, recovery can be difficult. This is because – unlike some amphibians and fish – humans lack the ability to produce enough new heart muscle cells to replace damaged tissue after a heart injury. In other words, the human heart cannot repair itself. Molecules known as messenger RNA (mRNA) carry the ‘instructions’ from the DNA inside the cell nucleus to its protein-making machinery in the cytoplasm of the cell. These messenger molecules can also be altered by different enzymes that attach or remove chemical groups. These modifications can change the stability of the mRNA, or even ‘silence’ it altogether by stopping it from interacting with the protein-making machinery, thus halting production of the protein it encodes. For example, a protein called Mettl3 can attach a methyl group to a specific part of the mRNA, causing a reversible mRNA modification known as m6A. This type of alteration has been shown to play a role in many conditions, including heart disease, but it has been unclear whether m6A could also be important for the regeneration of heart tissue. To find out more, Jiang, Liu, Chen et al. studied heart injury in mice of various ages. Newborn mice can regenerate their heart muscle for a short time, but adult mice lack this ability, which makes them a useful model to study heart disease. Analyses of the proteins and mRNAs in mouse heart cells confirmed that both Me...