Species-specific formation of paraspeckles in intestinal epithelium revealed by characterization of <i>NEAT1</i> in naked mole-rat

Abstract

Paraspeckles are mammalian-specific nuclear bodies built on the long noncoding RNA <i>NEAT1_2</i> 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 <i>NEAT1_2</i> in naked mole-rats (n<i>NEAT1_2</i>), which exhibit extreme longevity and lower susceptibility to cancer. In the intestine, n<i>NEAT1_2</i> is widely expressed along the entire intestinal epithelium, which is different from the expression of m<i>Neat1_2</i> 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<i>NEAT1_2</i> recruits a different set of RNA binding proteins in a cell type-specific manner during the formation of paraspeckles in different organisms.