hnRNP U 核内不均一核糖核蛋白是 Xist RNA 染色体定位所必需的。

The matrix protein hnRNP U is required for chromosomal localization of Xist RNA.

机构信息

RNA Biology Laboratory, RIKEN Advanced Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

出版信息

Dev Cell. 2010 Sep 14;19(3):469-76. doi: 10.1016/j.devcel.2010.08.006.

DOI:10.1016/j.devcel.2010.08.006

PMID:20833368

Abstract

In XX female mammals, one of the two X chromosomes is epigenetically inactivated to equalize gene expression with XY males. The formation of the inactive X chromosome (Xi) is regulated by an X-linked long noncoding RNA Xist, which accumulates on the entire length of the chromosome in cis and induces heterochromatin formation. However, the mechanism by which Xist RNA "paints" the Xi has long remained elusive. Here, we show that a matrix protein hnRNP U/SP120/SAF-A is required for the accumulation of Xist RNA on the Xi. Xist RNA and hnRNP U interact and upon depletion of hnRNP U, Xist RNA is detached from the Xi and diffusely localized into the nucleoplasm. In addition, ES cells lacking hnRNP U expression fail to form the Xi. We propose that the association with matrix proteins is an essential step in the epigenetic regulation of gene expression by Xist RNA.

摘要

在 XX 雌性哺乳动物中，两条 X 染色体中的一条通过表观遗传失活来与 XY 雄性的基因表达达到平衡。失活 X 染色体 (Xi) 的形成受 X 连锁的长非编码 RNA Xist 调控，该 RNA 在顺式上积累在整条染色体上，并诱导异染色质形成。然而，Xist RNA“标记”Xi 的机制长期以来一直难以捉摸。在这里，我们表明基质蛋白 hnRNP U/SP120/SAF-A 对于 Xist RNA 在 Xi 上的积累是必需的。Xist RNA 与 hnRNP U 相互作用，并且在 hnRNP U 耗尽时，Xist RNA 从 Xi 上脱离并弥散到核质中。此外，缺乏 hnRNP U 表达的 ES 细胞无法形成 Xi。我们提出，与基质蛋白的结合是 Xist RNA 对基因表达进行表观遗传调控的一个必要步骤。