Shichino Yuichi, Yamashita Akira, Yamamoto Masayuki
Laboratory of Gene Function, Kazusa DNA Research Institute, 2-6-7 Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan.
Laboratory of Gene Function, Kazusa DNA Research Institute, 2-6-7 Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan Laboratory of Cell Responses, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan
Open Biol. 2014 Jun;4(6):140022. doi: 10.1098/rsob.140022.
Long non-coding RNAs (lncRNAs) play key roles in the formation of nuclear bodies. In the fission yeast Schizosaccharomyces pombe, a lncRNA species termed meiRNA forms a nuclear dot structure at its own genetic locus, the sme2 locus, with its protein-binding partner Mei2. This dot structure, called Mei2 dot, promotes the progression of meiosis by suppressing Mmi1, a crucial factor involved in the selective elimination of meiosis-specific transcripts. The meiRNA itself is a target of Mmi1-mediated elimination and is supposed to function as a decoy to lure Mmi1. However, detailed mechanisms underlying the formation of Mei2 dot and inactivation of Mmi1 remain ambiguous. Here, we show that the localization of meiRNA, at its genetic locus sme2, depends on its association with Mmi1. We also demonstrate that one of the multiple Mmi1 foci in mitotic cells localizes to the sme2 locus. Furthermore, the overexpression of meiRNA promotes the accumulation of Mmi1 to the sme2 locus even in the absence of Mei2 and reduces the activity of Mmi1. These findings indicate that the retention of meiRNA at its genetic locus is facilitated by Mmi1, which then attracts scattered Mmi1 to inhibit its function.
长链非编码RNA（lncRNAs）在核体形成过程中发挥关键作用。在裂殖酵母粟酒裂殖酵母中，一种名为meiRNA的lncRNA在其自身的基因位点sme2处与蛋白质结合伴侣Mei2形成核点结构。这种被称为Mei2点的结构通过抑制Mmi1来促进减数分裂进程，Mmi1是参与选择性消除减数分裂特异性转录本的关键因子。meiRNA本身是Mmi1介导消除的靶标，并且被认为作为诱饵来吸引Mmi1。然而，Mei2点形成和Mmi1失活的详细机制仍不明确。在此，我们表明meiRNA在其基因位点sme2处的定位取决于它与Mmi1的结合。我们还证明有丝分裂细胞中多个Mmi1焦点之一定位于sme2位点。此外，即使在没有Mei2的情况下，meiRNA的过表达也会促进Mmi1在sme2位点的积累，并降低Mmi1的活性。这些发现表明Mmi1促进了meiRNA在其基因位点的保留，然后吸引分散的Mmi1以抑制其功能。
