Protein synthesis generally starts with a methionine that is removed during translation. However, cytoplasmic actin defies this rule because its synthesis involves noncanonical excision of the acetylated methionine by an unidentified enzyme after translation. Here, we identified C19orf54, named ACTMAP (actin maturation protease), as this enzyme. Its ablation resulted in viable mice in which the cytoskeleton was composed of immature actin molecules across all tissues. However, in skeletal muscle, the lengths of sarcomeric actin filaments were shorter, muscle function was decreased, and centralized nuclei, a common hallmark of myopathies, progressively accumulated. Thus, ACTMAP encodes the missing factor required for the synthesis of mature actin and regulates specific actin-dependent traits in vivo.

中文翻译：

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肌动蛋白成熟需要 ACTMAP/C19orf54 蛋白酶

蛋白质合成通常从翻译过程中去除的蛋氨酸开始。然而，细胞质肌动蛋白违反了这一规则，因为它的合成涉及翻译后通过一种不明酶对乙酰化蛋氨酸的非规范切除。在这里，我们确定了 C19orf54，命名为 ACTMAP（肌动蛋白成熟蛋白酶），作为这种酶。它的消融产生了可存活的小鼠，其中细胞骨架由所有组织中的未成熟肌动蛋白分子组成。然而，在骨骼肌中，肌节肌动蛋白丝的长度变短，肌肉功能下降，并且作为肌病的常见标志的集中核逐渐积累。因此，ACTMAP 编码成熟肌动蛋白合成所需的缺失因子，并在体内调节特定的肌动蛋白依赖性特征。