MxB inhibits long interspersed element type 1 retrotransposition.

Long interspersed element type 1 (LINE-1, also L1 for short) is the only autonomously transposable element in the human genome. Its insertion into a new genomic site may disrupt the function of genes, potentially causing genetic diseases. Cells have thus evolved a battery of mechanisms to tightly co...

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Main Authors: Yu Huang, Fengwen Xu, Shan Mei, Xiaoman Liu, Fei Zhao, Liang Wei, Zhangling Fan, Yamei Hu, Liming Wang, Bin Ai, Shan Cen, Chen Liang, Fei Guo
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-02-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1010034
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author Yu Huang
Fengwen Xu
Shan Mei
Xiaoman Liu
Fei Zhao
Liang Wei
Zhangling Fan
Yamei Hu
Liming Wang
Bin Ai
Shan Cen
Chen Liang
Fei Guo
author_facet Yu Huang
Fengwen Xu
Shan Mei
Xiaoman Liu
Fei Zhao
Liang Wei
Zhangling Fan
Yamei Hu
Liming Wang
Bin Ai
Shan Cen
Chen Liang
Fei Guo
author_sort Yu Huang
collection DOAJ
description Long interspersed element type 1 (LINE-1, also L1 for short) is the only autonomously transposable element in the human genome. Its insertion into a new genomic site may disrupt the function of genes, potentially causing genetic diseases. Cells have thus evolved a battery of mechanisms to tightly control LINE-1 activity. Here, we report that a cellular antiviral protein, myxovirus resistance protein B (MxB), restricts the mobilization of LINE-1. This function of MxB requires the nuclear localization signal located at its N-terminus, its GTPase activity and its ability to form oligomers. We further found that MxB associates with LINE-1 protein ORF1p and promotes sequestration of ORF1p to G3BP1-containing cytoplasmic granules. Since knockdown of stress granule marker proteins G3BP1 or TIA1 abolishes MxB inhibition of LINE-1, we conclude that MxB engages stress granule components to effectively sequester LINE-1 proteins within the cytoplasmic granules, thus hindering LINE-1 from accessing the nucleus to complete retrotransposition. Thus, MxB protein provides one mechanism for cells to control the mobility of retroelements.
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spelling doaj.art-75a16fde995f4a6c9e793ee9f5b59a8d2022-12-21T19:29:34ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-02-01182e101003410.1371/journal.pgen.1010034MxB inhibits long interspersed element type 1 retrotransposition.Yu HuangFengwen XuShan MeiXiaoman LiuFei ZhaoLiang WeiZhangling FanYamei HuLiming WangBin AiShan CenChen LiangFei GuoLong interspersed element type 1 (LINE-1, also L1 for short) is the only autonomously transposable element in the human genome. Its insertion into a new genomic site may disrupt the function of genes, potentially causing genetic diseases. Cells have thus evolved a battery of mechanisms to tightly control LINE-1 activity. Here, we report that a cellular antiviral protein, myxovirus resistance protein B (MxB), restricts the mobilization of LINE-1. This function of MxB requires the nuclear localization signal located at its N-terminus, its GTPase activity and its ability to form oligomers. We further found that MxB associates with LINE-1 protein ORF1p and promotes sequestration of ORF1p to G3BP1-containing cytoplasmic granules. Since knockdown of stress granule marker proteins G3BP1 or TIA1 abolishes MxB inhibition of LINE-1, we conclude that MxB engages stress granule components to effectively sequester LINE-1 proteins within the cytoplasmic granules, thus hindering LINE-1 from accessing the nucleus to complete retrotransposition. Thus, MxB protein provides one mechanism for cells to control the mobility of retroelements.https://doi.org/10.1371/journal.pgen.1010034
spellingShingle Yu Huang
Fengwen Xu
Shan Mei
Xiaoman Liu
Fei Zhao
Liang Wei
Zhangling Fan
Yamei Hu
Liming Wang
Bin Ai
Shan Cen
Chen Liang
Fei Guo
MxB inhibits long interspersed element type 1 retrotransposition.
PLoS Genetics
title MxB inhibits long interspersed element type 1 retrotransposition.
title_full MxB inhibits long interspersed element type 1 retrotransposition.
title_fullStr MxB inhibits long interspersed element type 1 retrotransposition.
title_full_unstemmed MxB inhibits long interspersed element type 1 retrotransposition.
title_short MxB inhibits long interspersed element type 1 retrotransposition.
title_sort mxb inhibits long interspersed element type 1 retrotransposition
url https://doi.org/10.1371/journal.pgen.1010034
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