Wang Qiaoqiao, Zhang Zuo, Blackwell Katherine, Carmichael Gordon G
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030 USA.
Curr Biol. 2005 Feb 22;15(4):384-91. doi: 10.1016/j.cub.2005.01.046.
The fate of double-stranded RNA (dsRNA) in the cell depends on both its length and location . The expression of dsRNA in the nucleus leads to several distinct consequences. First, the promiscuous deamination of adenosines to inosines by dsRNA-specific adenosine deaminase (ADAR) can lead to the nuclear retention of edited transcripts . Second, dsRNAs might induce heterochromatic gene silencing through an RNAi-related mechanism . Is RNA editing also connected to heterochromatin? We report that members of the conserved Vigilin class of proteins have a high affinity for inosine-containing RNAs. In agreement with other work , we find that these proteins localize to heterochromatin and that mutation or depletion of the Drosophila Vigilin, DDP1, leads to altered nuclear morphology and defects in heterochromatin and chromosome segregation. Furthermore, nuclear Vigilin is found in complexes containing not only the editing enzyme ADAR1 but also RNA helicase A and Ku86/70. In the presence of RNA, the Vigilin complex recruits the DNA-PKcs enzyme, which appears to phosphorylate a discrete set of targets, some or all of which are known to participate in chromatin silencing. These results are consistent with a mechanistic link between components of the DNA-repair machinery and RNA-mediated gene silencing.
细胞中双链RNA（dsRNA）的命运取决于其长度和位置。dsRNA在细胞核中的表达会导致几种不同的结果。首先，dsRNA特异性腺苷脱氨酶（ADAR）将腺苷随机脱氨为肌苷，可导致编辑后的转录本滞留于细胞核。其次，dsRNA可能通过一种与RNA干扰相关的机制诱导异染色质基因沉默。RNA编辑也与异染色质有关吗？我们报道，保守的Vigilin类蛋白质成员对含肌苷的RNA具有高亲和力。与其他研究一致，我们发现这些蛋白质定位于异染色质，果蝇Vigilin（DDP1）的突变或缺失会导致核形态改变以及异染色质和染色体分离缺陷。此外，在细胞核中发现的Vigilin不仅存在于含有编辑酶ADAR1的复合物中，还存在于含有RNA解旋酶A和Ku86/70的复合物中。在有RNA存在的情况下，Vigilin复合物募集DNA-PKcs酶，该酶似乎会磷酸化一组特定的靶点，其中一些或全部已知参与染色质沉默。这些结果与DNA修复机制的组成部分和RNA介导的基因沉默之间的机制联系是一致的。
