Abstract
Neat1 is a long noncoding RNA (lncRNA) that serves as an architectural component of the nuclear bodies known as paraspeckles. Two isoforms of Neat1, the short isoform Neat1_1 and the long isoform Neat1_2, are generated from the same gene locus by alternative 3′ processing. Neat1_1 is the most abundant and the best conserved isoform expressed in various cell types, whereas Neat1_2 is expressed in a small population of particular cell types, including the tip cells of the intestinal epithelium. To investigate the physiological significance of isoform switching, we created mutant mice that solely expressed Neat1_2 by deleting the upstream polyadenylation (poly-A) signal (PAS) required for the production of Neat1_1. We observed the loss of Neat1_1 and strong up-regulation of Neat1_2 in various tissues and cells and the subsequent hyperformation of paraspeckles, especially in cells that normally express Neat1_2. However, the mutant mice were born at the expected Mendelian ratios and did not exhibit obvious external and histological abnormalities. These observations suggested that the hyperformation of paraspeckles does not interfere with the development and growth of these animals under normal laboratory conditions.
Highlights
Many long noncoding RNAs are transcribed from the genome, and these transcripts regulate various molecular and cellular processes, including the epigenetic control of gene expression, mRNA processing, and the formation of nonmembranous cellular bodies (Long et al 2017)
Enhanced formation of paraspeckles was observed in cells that endogenously express Neat1_2, including the tip cells in the intestinal epithelium and liver cells
Despite the hyperformation of paraspeckles in various cell types, Neat1ΔPAS/ΔPAS mice were born at the expected Mendelian ratios and did not exhibit any obvious external or histological abnormalities
Summary
Many long noncoding RNAs (lncRNA) are transcribed from the genome, and these transcripts regulate various molecular and cellular processes, including the epigenetic control of gene expression, mRNA processing, and the formation of nonmembranous cellular bodies (Long et al 2017). Neat is one of the best-studied functionally validated lncRNAs and serves as an architectural component of the nuclear bodies known as paraspeckles (Chen and Carmichael 2009; Clemson et al 2009; Sasaki et al 2009; Sunwoo et al 2009). Paraspeckles are phase-separated nonmembranous nuclear bodies that are unique to mammalian species (Fox et al 2018; Nakagawa et al 2018).
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