Functional RNomics Team; Biomedicinal Information Research Center; National Institute of Advanced Industrial Science and Technology (AIST); Koutou, Tokyo, Japan.
RNA Biol. 2013 Mar;10(3):456-61. doi: 10.4161/rna.23547. Epub 2013 Jan 16.
Paraspeckles are unique subnuclear structures that are built around a specific long non-coding RNA (lncRNA), NEAT1, which is comprised of two isoforms (NEAT1_1 and NEAT1_2) that are produced by alternative 3'-end processing. NEAT1 lncRNAs are unusual RNA polymerase II transcripts that lack introns. The non-polyadenylated 3'-end of NEAT1_2 is non-canonically processed by RNase P. NEAT1_2 is an essential component for paraspeckle formation. Paraspeckles form during the NEAT1_2 lncRNA biogenesis process, which encompasses transcription from its own chromosome locus through lncRNA processing and accumulation. Recent RNAi analyses of 40 paraspeckle proteins (PSPs) identified four PSPs that are required for paraspeckle formation by mediating NEAT1 processing and accumulation. In particular, HNRNPK was shown to arrest CFIm-dependent NEAT1_1 polyadenylation, leading to NEAT1_2 synthesis. The other three PSPs were required for paraspeckle formation, but did not affect NEAT1_2 expression. This observation suggests that NEAT1_2 accumulation is necessary but not sufficient for paraspeckle formation. An additional step, presumably the bundling of NEAT1 ribonucleoprotein sub-complexes, may be required for construction of the intact paraspeckle structure. NEAT1 expression is likely regulated at transcriptional and post-transcriptional steps under certain stress conditions, suggesting roles for paraspeckles in the lncRNA-mediated regulation of gene expression, such as the nucleocytoplasmic transport of mRNA in response to certain stimuli.
核内斑是一种独特的亚核结构，围绕着一种特定的长链非编码 RNA（lncRNA）构建，即 NEAT1。NEAT1 由两个异构体（NEAT1_1 和 NEAT1_2）组成，它们通过 3'-末端的选择性加工产生。NEAT1 lncRNAs 是缺乏内含子的不寻常 RNA 聚合酶 II 转录物。NEAT1_2 的非多聚腺苷酸化 3'-末端通过 RNase P 进行非常规加工。NEAT1_2 是形成核内斑的必需成分。核内斑在 NEAT1_2 lncRNA 生物发生过程中形成，该过程包括从其自身染色体基因座转录、lncRNA 加工和积累。最近对 40 种核内斑蛋白（PSPs）的 RNAi 分析鉴定了四个 PSP，它们通过介导 NEAT1 加工和积累来形成核内斑。特别是，HNRNPK 被证明通过阻止 CFIm 依赖性的 NEAT1_1 多聚腺苷酸化来阻止 NEAT1_2 的合成。另外三个 PSP 对于核内斑的形成是必需的，但不影响 NEAT1_2 的表达。这一观察结果表明，NEAT1_2 的积累对于核内斑的形成是必要的，但不是充分的。可能需要一个额外的步骤，大概是 NEAT1 核糖核蛋白亚复合物的捆绑，以便构建完整的核内斑结构。在某些应激条件下，NEAT1 的表达可能受到转录和转录后步骤的调节，这表明核内斑在 lncRNA 介导的基因表达调控中发挥作用，例如在某些刺激下 mRNA 的核质转运。
