Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
Cell Rep. 2016 Feb 23;14(7):1684-1697. doi: 10.1016/j.celrep.2016.01.039. Epub 2016 Feb 11.
A fundamental principle governing organ size and function is the fine balance between cell proliferation and cell differentiation. Here, we identify RONIN (THAP11) as a key transcriptional regulator of retinal progenitor cell (RPC) proliferation. RPC-specific loss of Ronin results in a phenotype strikingly similar to that resulting from the G1- to S-phase arrest and photoreceptor degeneration observed in the Cyclin D1 null mutants. However, we determined that, rather than regulating canonical cell-cycle genes, RONIN regulates a cohort of mitochondrial genes including components of the electron transport chain (ETC), which have been recently implicated as direct regulators of the cell cycle. Coincidentally, with premature cell-cycle exit, Ronin mutants exhibited deficient ETC activity, reduced ATP levels, and increased oxidative stress that we ascribe to specific loss of subunits within complexes I, III, and IV. These data implicate RONIN as a positive regulator of mitochondrial gene expression that coordinates mitochondrial activity and cell-cycle progression.
一个控制器官大小和功能的基本原则是细胞增殖和细胞分化之间的精细平衡。在这里，我们确定 RONIN（THAP11）是视网膜祖细胞（RPC）增殖的关键转录调节因子。RPC 特异性的 Ronin 缺失导致的表型与 Cyclin D1 缺失突变体中观察到的 G1 到 S 期阻滞和光感受器退化非常相似。然而，我们确定，RONIN 调节的是一群线粒体基因，包括电子传递链（ETC）的组成部分，这些基因最近被认为是细胞周期的直接调节因子。巧合的是，随着细胞周期的过早退出，Ronin 突变体表现出 ETC 活性降低、ATP 水平降低和氧化应激增加，我们将其归因于复合物 I、III 和 IV 中的亚基特异性缺失。这些数据表明 RONIN 是线粒体基因表达的正调节剂，它协调线粒体活性和细胞周期进程。
