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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2021
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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) |
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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 |
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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 AT shizukanohara characterizationofanactiveline1inthenakedmoleratgenome AT yukinishikawa characterizationofanactiveline1inthenakedmoleratgenome AT yusukesuzuki characterizationofanactiveline1inthenakedmoleratgenome AT yoshimikawamura characterizationofanactiveline1inthenakedmoleratgenome AT kyokomiura characterizationofanactiveline1inthenakedmoleratgenome AT keizotomonaga characterizationofanactiveline1inthenakedmoleratgenome AT keijiueda characterizationofanactiveline1inthenakedmoleratgenome AT tomoyukihonda characterizationofanactiveline1inthenakedmoleratgenome |
_version_ |
1718392749805273088 |