Species-specific formation of paraspeckles in intestinal epithelium revealed by characterization of NEAT1 in naked mole-rat
- Akihiro Yamada1,
- Hikaru Toya1,
- Mayuko Tanahashi1,
- Misuzu Kurihara1,
- Mari Mito2,
- Shintaro Iwasaki2,3,
- Satoshi Kurosaka4,
- Toru Takumi4,5,
- Archa Fox6,7,8,
- Yoshimi Kawamura9,10,
- Kyoko Miura9,10 and
- Shinichi Nakagawa1
- 1RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
- 2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama 351-0198, Japan
- 3Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan
- 4RIKEN Brain Science Institute, Saitama 351-0198, Japan
- 5Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe 670-0017, Japan
- 6School of Human Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia
- 7Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia
- 8School of Molecular Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia
- 9Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
- 10Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto 860-8556, Japan
- Corresponding author: nakagawas{at}pharm.hokudai.ac.jp
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 a different set of RNA binding proteins in a cell type-specific manner during the formation of paraspeckles in different organisms.
Keywords
- Received February 17, 2022.
- Accepted May 30, 2022.
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