RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama 351-0198, Japan.
RNA. 2022 Aug;28(8):1128-1143. doi: 10.1261/rna.079135.122. Epub 2022 Jun 2.
Paraspeckles are mammalian-specific nuclear bodies built on the long noncoding RNA 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 in naked mole-rats (n), which exhibit extreme longevity and lower susceptibility to cancer. In the intestine, n is widely expressed along the entire intestinal epithelium, which is different from the expression of m 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 n recruits a different set of RNA binding proteins in a cell type-specific manner during the formation of paraspeckles in different organisms.
核内体是哺乳动物特有的核体，构建在长链非编码 RNA 上。核内体形成的分子机制主要在人类或小鼠细胞中进行了研究，目前尚不清楚在其他哺乳动物物种中形成核内体是否涉及相同的分子成分。因此，我们研究了在裸鼹鼠（n）中 的表达模式，裸鼹鼠表现出极端的长寿和较低的癌症易感性。在肠道中，n 广泛表达于整个肠道上皮细胞，这与 m 的表达模式不同，m 在小鼠中仅局限于远端细胞。值得注意的是，在裸鼹鼠的肠道上皮细胞的远端部分缺乏 FUS，一种对于人类和小鼠中核内体形成至关重要的 FET 家族 RNA 结合蛋白。相反，其他 FET 家族蛋白 EWSR1 和 TAF15 的 mRNAs 在远端区域表达。在 Fus 缺陷型鼠胚胎成纤维细胞中表达这些蛋白质可挽救核内体的形成。这些观察结果表明，n 在不同生物体中以细胞类型特异性的方式募集了一组不同的 RNA 结合蛋白来形成核内体。
