Chigi Yuta, Sasaki Hiroyuki, Sado Takashi
Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, 3327-204, Nakamachi, Nara 631-8505, Japan.
Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
RNA. 2017 Dec;23(12):1894-1901. doi: 10.1261/rna.062158.117. Epub 2017 Sep 22.
X inactive-specific transcript () is a long noncoding RNA that plays an essential role in X chromosome inactivation. Although RNA, like common protein-coding mRNAs, is transcribed by RNA polymerase II, spliced and polyadenylated, it is retained in the nucleus and associates with the X chromosome it originates from. It has been assumed that RNA recruits proteins involved in epigenetic modifications and chromatin compaction to the X chromosome. One of the major proteins constituting the nuclear matrix, hnRNP U, has been shown to be required for the association of RNA with the inactive X chromosome (Xi). In this study, we found that the first 950-nt sequence of RNA had the potential to associate with chromatin in a manner independent of hnRNP U. Furthermore, its chromatin association is apparently dependent on the presence of an intact A-repeat sequence, which is one of the repeats in / RNA conserved among many mammalian species, and has been shown to be important for RNA-mediated silencing. Taking this unexpected finding and a previous study demonstrating the effect of RNA lacking the A-repeat on the formation of the silent heterochromatin domain together, we suggest that the A-repeat captures chromatin near the initial loading site of RNA and relocates it into the core of the heterochromatin domain.
X染色体失活特异性转录本（Xist）是一种长链非编码RNA，在X染色体失活过程中发挥着至关重要的作用。尽管Xist RNA与常见的蛋白质编码mRNA一样，由RNA聚合酶II转录、剪接并进行多聚腺苷酸化，但它保留在细胞核中，并与它所起源的X染色体相关联。据推测，Xist RNA会将参与表观遗传修饰和染色质压缩的蛋白质招募到X染色体上。构成核基质的主要蛋白质之一，即核不均一核糖核蛋白U（hnRNP U），已被证明是Xist RNA与失活X染色体（Xi）关联所必需的。在本研究中，我们发现Xist RNA的前950个核苷酸序列有潜力以一种独立于hnRNP U的方式与染色质相关联。此外，其与染色质的关联显然依赖于完整A重复序列的存在，A重复序列是许多哺乳动物物种中Xist RNA保守的重复序列之一，并且已被证明对Xist RNA介导的沉默很重要。综合这一意外发现以及先前一项证明缺乏A重复序列的Xist RNA对沉默异染色质结构域形成有影响的研究，我们认为A重复序列在Xist RNA的初始加载位点附近捕获染色质，并将其重新定位到异染色质结构域的核心。
