Actin R256 mono-methylation is a conserved post-translational modification involved in transcription

Nuclear actin has been elusive due to the lack of molecular mechanisms. From actin-containing chromatin remodeling complexes, we discovered an arginine mono-methylation mark on evolutionarily conserved R256 residue of actin (R256me1). Actin R256 mutations in yeast affect nuclear functions, and cause diseases in human. Interestingly, we show that an antibody specific for actin R256me1 preferentially stain nuclear actin over cytoplasmic actin in yeast, mouse and human cells. We also show that actin R256me1 is regulated by protein arginine methyl transferase-5 (PRMT5) in HEK293 cells. Genome-wide survey of actin R256me1 mark provides a landscape for nuclear actin correlated with transcription. Further gene expression and protein interaction studies uncover extensive correlations between actin R256me1 and active transcription. The discovery of actin R256me1 mark suggests a fundamental mechanism to distinguish nuclear actin from cytoplasmic actin through post-translational modification (PTM), and potentially implicates an actin PTM mark in transcription and human diseases.由于缺乏相关分子机制，核肌动蛋白的相关研究长期以来难以阐明。我们从含肌动蛋白的染色质重塑复合物中，发现了肌动蛋白进化保守位点R256上的精氨酸单甲基化修饰标记（R256me1）。酵母中肌动蛋白R256位点的突变会影响细胞核功能，并可引发人类疾病。有趣的是，我们证实，针对肌动蛋白R256me1的特异性抗体，在酵母、小鼠及人类细胞中可优先标记核肌动蛋白，而非细胞质肌动蛋白。我们还证实，在HEK293细胞中，肌动蛋白R256me1的修饰受蛋白质精氨酸甲基转移酶5（PRMT5）调控。对肌动蛋白R256me1标记进行全基因组分析，可绘制出与转录过程相关的核肌动蛋白调控图谱。进一步的基因表达与蛋白质相互作用研究揭示，肌动蛋白R256me1与活跃转录过程存在广泛关联。肌动蛋白R256me1修饰标记的发现，提出了一种通过翻译后修饰（PTM）区分核肌动蛋白与细胞质肌动蛋白的核心机制，同时也暗示肌动蛋白的翻译后修饰标记可能参与转录过程及人类疾病的发生发展。