近年来，N 6 -甲基腺苷(m 6 A)对RNA的修饰作为基因调控的一般机制引起了人们的关注。在肝脏中，m 6 A 及其相关机制已被研究为疾病和癌症的潜在生物标志物，对新陈代谢、细胞周期调节和促癌状态信号传导具有影响。然而，这些观察数据尚未在体内进行因果检验。例如，关键 m 6 A 写入器 Mettl3 和 Mettl14 以及 m 6 A 读取器 Ythdf1 和 Ythdf2 的扰动都没有像体外那样在体内得到彻底的机械表征。为了了解这些机制的功能，我们开发了小鼠模型，发现删除 Mettl14 会导致以核异型为特征的进行性肝损伤，mRNA 剪接、加工和输出的变化导致 mRNA 监视和回收的增加。

Modification of RNA with N 6 -methyladenosine (m 6 A) has gained attention in recent years as a general mechanism of gene regulation. In the liver, m 6 A, along with its associated machinery, has been studied as a potential biomarker of disease and cancer, with impacts on metabolism, cell cycle regulation, and pro-cancer state signaling. However these observational data have yet to be causally examined in vivo. For example, neither perturbation of the key m 6 A writers Mettl3 and Mettl14 , nor the m 6 A readers Ythdf1 and Ythdf2 have been thoroughly mechanistically characterized in vivo as they have been in vitro . To understand the functions of these machineries, we developed mouse models and found that deleting Mettl14 led to progressive liver injury characterized by nuclear heterotypia, with changes in mRNA splicing, processing and export leading to increases in mRNA surveillance and recycling.