Characterization of an active LINE-1 in the naked mole-rat genome

Abstract Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-living rodent species. A reason for their long lifespan is pronounced cancer resistance. Therefore, researchers believe that NMRs have unknown secrets of cancer resistance and seek to find them. Here, to reveal the secrets, we no...

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Autores principales: Shunichi Yamaguchi, Shizuka Nohara, Yuki Nishikawa, Yusuke Suzuki, Yoshimi Kawamura, Kyoko Miura, Keizo Tomonaga, Keiji Ueda, Tomoyuki Honda
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/9573c7f2bbc149f08260c1f6a02392b8
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spelling oai:doaj.org-article:9573c7f2bbc149f08260c1f6a02392b82021-12-02T13:34:45ZCharacterization of an active LINE-1 in the naked mole-rat genome10.1038/s41598-021-84962-82045-2322https://doaj.org/article/9573c7f2bbc149f08260c1f6a02392b82021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84962-8https://doaj.org/toc/2045-2322Abstract Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-living rodent species. A reason for their long lifespan is pronounced cancer resistance. Therefore, researchers believe that NMRs have unknown secrets of cancer resistance and seek to find them. Here, to reveal the secrets, we noticed a retrotransposon, long interspersed nuclear element 1 (L1). L1s can amplify themselves and are considered endogenous oncogenic mutagens. Since the NMR genome contains fewer L1-derived sequences than other mammalian genomes, we reasoned that the retrotransposition activity of L1s in the NMR genome is lower than those in other mammalian genomes. In this study, we successfully cloned an intact L1 from the NMR genome and named it NMR-L1. An L1 retrotransposition assay using the NMR-L1 reporter revealed that NMR-L1 was active retrotransposon, but its activity was lower than that of human and mouse L1s. Despite lower retrotrasposition activity, NMR-L1 was still capable of inducing cell senescence, a tumor-protective system. NMR-L1 required the 3′ untranslated region (UTR) for retrotransposition, suggesting that NMR-L1 is a stringent-type of L1. We also confirmed the 5′ UTR promoter activity of NMR-L1. Finally, we identified the G-quadruplex structure of the 3′ UTR, which modulated the retrotransposition activity of NMR-L1. Taken together, the data indicate that NMR-L1 retrotranspose less efficiently, which may contribute to the cancer resistance of NMRs.Shunichi YamaguchiShizuka NoharaYuki NishikawaYusuke SuzukiYoshimi KawamuraKyoko MiuraKeizo TomonagaKeiji UedaTomoyuki HondaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shunichi Yamaguchi
Shizuka Nohara
Yuki Nishikawa
Yusuke Suzuki
Yoshimi Kawamura
Kyoko Miura
Keizo Tomonaga
Keiji Ueda
Tomoyuki Honda
Characterization of an active LINE-1 in the naked mole-rat genome
description Abstract Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-living rodent species. A reason for their long lifespan is pronounced cancer resistance. Therefore, researchers believe that NMRs have unknown secrets of cancer resistance and seek to find them. Here, to reveal the secrets, we noticed a retrotransposon, long interspersed nuclear element 1 (L1). L1s can amplify themselves and are considered endogenous oncogenic mutagens. Since the NMR genome contains fewer L1-derived sequences than other mammalian genomes, we reasoned that the retrotransposition activity of L1s in the NMR genome is lower than those in other mammalian genomes. In this study, we successfully cloned an intact L1 from the NMR genome and named it NMR-L1. An L1 retrotransposition assay using the NMR-L1 reporter revealed that NMR-L1 was active retrotransposon, but its activity was lower than that of human and mouse L1s. Despite lower retrotrasposition activity, NMR-L1 was still capable of inducing cell senescence, a tumor-protective system. NMR-L1 required the 3′ untranslated region (UTR) for retrotransposition, suggesting that NMR-L1 is a stringent-type of L1. We also confirmed the 5′ UTR promoter activity of NMR-L1. Finally, we identified the G-quadruplex structure of the 3′ UTR, which modulated the retrotransposition activity of NMR-L1. Taken together, the data indicate that NMR-L1 retrotranspose less efficiently, which may contribute to the cancer resistance of NMRs.
format article
author Shunichi Yamaguchi
Shizuka Nohara
Yuki Nishikawa
Yusuke Suzuki
Yoshimi Kawamura
Kyoko Miura
Keizo Tomonaga
Keiji Ueda
Tomoyuki Honda
author_facet Shunichi Yamaguchi
Shizuka Nohara
Yuki Nishikawa
Yusuke Suzuki
Yoshimi Kawamura
Kyoko Miura
Keizo Tomonaga
Keiji Ueda
Tomoyuki Honda
author_sort Shunichi Yamaguchi
title Characterization of an active LINE-1 in the naked mole-rat genome
title_short Characterization of an active LINE-1 in the naked mole-rat genome
title_full Characterization of an active LINE-1 in the naked mole-rat genome
title_fullStr Characterization of an active LINE-1 in the naked mole-rat genome
title_full_unstemmed Characterization of an active LINE-1 in the naked mole-rat genome
title_sort characterization of an active line-1 in the naked mole-rat genome
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/9573c7f2bbc149f08260c1f6a02392b8
work_keys_str_mv AT shunichiyamaguchi characterizationofanactiveline1inthenakedmoleratgenome
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AT kyokomiura characterizationofanactiveline1inthenakedmoleratgenome
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