Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State

Frontiers in Cell and Developmental Biology

Takashi Sado¹  Saya Ichihara²  Ruka Matsuura²  Tatsuro Nakajima³ 

[1] Agricultural Technology and Innovation Research Institute, Kindai University, Nara, Japan;Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nara, Japan;Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan;

关键词: Xist RNA;    embryonic stem cells (ESCs);    X chromosome inactivation;    heterochromatin;    gene silencing;    RNA-FISH;   

DOI  :  10.3389/fcell.2021.751154

来源: DOAJ

【 摘 要 】

Non-coding Xist RNA plays an essential role in X chromosome inactivation (XCI) in female mammals. It coats the X chromosome in cis and mediates the recruitment of many proteins involved in gene silencing and heterochromatinization. The molecular basis of how Xist RNA initiates chromosomal silencing and what proteins participate in this process has been extensively studied and elucidated. Its involvement in the establishment and maintenance of the X-inactivated state is, however, less understood. The XistIVS allele we previously reported is peculiar in that it can initiate XCI but fails to establish the inactive state that is stably maintained and, therefore, may provide an opportunity to explore how Xist RNA contributes to establish a robust heterochromatin state. Here we demonstrate that ectopic splicing taking place to produce XistIVS RNA disturbs its function to properly establish stable XCI state. This finding warrants the potential of XistIVS RNA to provide further insight into our understanding of how Xist RNA contributes to establish sustainable heterochromatin.

【 授权许可】

Unknown