Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France.
University Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France.
Nat Commun. 2021 Feb 3;12(1):770. doi: 10.1038/s41467-021-21032-7.
Long non-coding RNAs (lncRNAs) contribute to the regulation of gene expression in response to intra- or extracellular signals but the underlying molecular mechanisms remain largely unexplored. Here, we identify an uncharacterized lncRNA as a central player in shaping the meiotic gene expression program in fission yeast. We report that this regulatory RNA, termed mamRNA, scaffolds the antagonistic RNA-binding proteins Mmi1 and Mei2 to ensure their reciprocal inhibition and fine tune meiotic mRNA degradation during mitotic growth. Mechanistically, mamRNA allows Mmi1 to target Mei2 for ubiquitin-mediated downregulation, and conversely enables accumulating Mei2 to impede Mmi1 activity, thereby reinforcing the mitosis to meiosis switch. These regulations also occur within a unique Mmi1-containing nuclear body, positioning mamRNA as a spatially-confined sensor of Mei2 levels. Our results thus provide a mechanistic basis for the mutual control of gametogenesis effectors and further expand our vision of the regulatory potential of lncRNAs.
长非编码 RNA（lncRNA）在响应细胞内或细胞外信号时有助于基因表达的调控，但潜在的分子机制在很大程度上仍未被探索。在这里，我们鉴定出一种未被描述的 lncRNA 作为塑造有丝分裂酵母减数分裂基因表达程序的核心参与者。我们报告称，这种调节 RNA 称为 mamRNA，支架拮抗 RNA 结合蛋白 Mmi1 和 Mei2，以确保它们的相互抑制，并在有丝分裂生长过程中精细调节减数分裂 mRNA 的降解。在机制上，mamRNA 允许 Mmi1 将 Mei2 作为泛素介导的下调的靶标，并且相反地使积累的 Mei2 能够阻碍 Mmi1 的活性，从而加强有丝分裂到减数分裂的转换。这些调节也发生在独特的含有 Mmi1 的核体内，使 mamRNA 成为 Mei2 水平的空间受限传感器。因此，我们的结果为配子发生效应物的相互控制提供了一个机制基础，并进一步扩展了我们对 lncRNA 调节潜力的认识。
