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

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...

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Main Authors: Ruka Matsuura, Tatsuro Nakajima, Saya Ichihara, Takashi Sado
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.751154/full
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author Ruka Matsuura
Tatsuro Nakajima
Saya Ichihara
Takashi Sado
Takashi Sado
author_facet Ruka Matsuura
Tatsuro Nakajima
Saya Ichihara
Takashi Sado
Takashi Sado
author_sort Ruka Matsuura
collection DOAJ
description 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.
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spelling doaj.art-b75d2ab5990543299de630b1d3fff2162022-12-21T18:33:56ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-10-01910.3389/fcell.2021.751154751154Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin StateRuka Matsuura0Tatsuro Nakajima1Saya Ichihara2Takashi Sado3Takashi Sado4Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nara, JapanMedical Institute of Bioregulation, Kyushu University, Fukuoka, JapanDepartment of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nara, JapanDepartment of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nara, JapanAgricultural Technology and Innovation Research Institute, Kindai University, Nara, JapanNon-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.https://www.frontiersin.org/articles/10.3389/fcell.2021.751154/fullXist RNAembryonic stem cells (ESCs)X chromosome inactivationheterochromatingene silencingRNA-FISH
spellingShingle Ruka Matsuura
Tatsuro Nakajima
Saya Ichihara
Takashi Sado
Takashi Sado
Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State
Frontiers in Cell and Developmental Biology
Xist RNA
embryonic stem cells (ESCs)
X chromosome inactivation
heterochromatin
gene silencing
RNA-FISH
title Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State
title_full Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State
title_fullStr Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State
title_full_unstemmed Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State
title_short Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State
title_sort ectopic splicing disturbs the function of xist rna to establish the stable heterochromatin state
topic Xist RNA
embryonic stem cells (ESCs)
X chromosome inactivation
heterochromatin
gene silencing
RNA-FISH
url https://www.frontiersin.org/articles/10.3389/fcell.2021.751154/full
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