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Species-Specific Formation of Paraspeckles in Intestinal Epithelium Revealed by Characterization of NEAT1 in Naked Mole-rat

Akihiro Yamada, Hikaru Toya, Mayuko Tanahashi, Misuzu Kurihara, Mari Mito, Shintaro Iwasaki, Satoshi Kurosaka, Toru Takumi, Archa Fox, Yoshimi Kawamura, Kyoko Miura, View ORCID ProfileShinichi Nakagawa
doi: https://doi.org/10.1101/2022.02.17.480918
Akihiro Yamada
1RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan
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Hikaru Toya
1RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan
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Mayuko Tanahashi
1RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan
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Misuzu Kurihara
1RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan
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Mari Mito
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
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Shintaro Iwasaki
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
3Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan
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Satoshi Kurosaka
4RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
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Toru Takumi
4RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
5Department of Physiology and Cell Biology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo, Kobe 670-0017, Japan
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Archa Fox
6School of Human Sciences, University of Western Australia, Crawley, Western Australia, 6009; Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia; School of Molecular Sciences, University of Western Australia, Crawley, Western Australia, 6009, Australia
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Yoshimi Kawamura
7Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
8Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto 860-8556, Japan
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Kyoko Miura
7Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
8Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto 860-8556, Japan
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Shinichi Nakagawa
1RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan
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  • ORCID record for Shinichi Nakagawa
  • For correspondence: nakagawas@pharm.hokudai.ac.jp
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Abstract

Paraspeckles are mammalian-specific nuclear bodies built on the long noncoding RNA NEAT1_2. The molecular mechanisms of paraspeckle formation have been mainly studied using human or mouse cells, and it is not known if the same molecular components are involved in the formation of paraspeckles in other mammalian species. We thus investigated the expression pattern of NEAT1_2 in naked mole-rats (nNEAT1_2), which exhibit extreme longevity and lower susceptibility to cancer. In the intestine, nNEAT1_2 is widely expressed along the entire intestinal epithelium, which is different from the expression of mNeat1_2, that is restricted to the cells of the distal tip in mice. Notably, the expression of FUS, a FET family RNA binding protein, essential for the formation of paraspeckles both in humans and mice, was absent in the distal part of the intestinal epithelium in naked mole-rats. Instead, mRNAs of other FET family proteins EWSR1 and TAF15 were expressed in the distal region. Exogenous expression of these proteins in Fus-deficient murine embryonic fibroblast cells rescued the formation of paraspeckles. These observations suggest that nNEAT1_2 recruits different set of RNA binding proteins in a cell type-specific manner during the formation of paraspeckles in different organisms.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 18, 2022.
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Species-Specific Formation of Paraspeckles in Intestinal Epithelium Revealed by Characterization of NEAT1 in Naked Mole-rat
Akihiro Yamada, Hikaru Toya, Mayuko Tanahashi, Misuzu Kurihara, Mari Mito, Shintaro Iwasaki, Satoshi Kurosaka, Toru Takumi, Archa Fox, Yoshimi Kawamura, Kyoko Miura, Shinichi Nakagawa
bioRxiv 2022.02.17.480918; doi: https://doi.org/10.1101/2022.02.17.480918
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Species-Specific Formation of Paraspeckles in Intestinal Epithelium Revealed by Characterization of NEAT1 in Naked Mole-rat
Akihiro Yamada, Hikaru Toya, Mayuko Tanahashi, Misuzu Kurihara, Mari Mito, Shintaro Iwasaki, Satoshi Kurosaka, Toru Takumi, Archa Fox, Yoshimi Kawamura, Kyoko Miura, Shinichi Nakagawa
bioRxiv 2022.02.17.480918; doi: https://doi.org/10.1101/2022.02.17.480918

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