Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań 61-704, Poland.
Department of Biosciences, University of Oslo, Oslo 0316, Norway.
Nucleic Acids Res. 2022 Aug 12;50(14):8226-8239. doi: 10.1093/nar/gkac609.
Regnase-1 is an evolutionarily conserved endoribonuclease. It degrades diverse mRNAs important for many biological processes including immune homeostasis, development and cancer. There are two competing models of Regnase-1-mediated mRNA silencing. One model postulates that Regnase-1 works together with another RNA-binding protein, Roquin-1, which recruits Regnase-1 to specific mRNAs. The other model proposes that the two proteins function separately. Studying REGE-1, the Caenorhabditis elegans ortholog of Regnase-1, we have uncovered its functional relationship with RLE-1, the nematode counterpart of Roquin-1. While both proteins are essential for mRNA silencing, REGE-1 and RLE-1 appear to associate with target mRNA independently of each other. Thus, although the functional interdependence between REGE-1/Regnase-1 and RLE-1/Roquin-1 is conserved, the underlying mechanisms may display species-specific variation, providing a rare perspective on the evolution of this important post-transcriptional regulatory mechanism.
Regnase-1 是一种进化上保守的内切核糖核酸酶。它降解多种对包括免疫稳态、发育和癌症在内的许多生物学过程很重要的 mRNA。Regnase-1 介导的 mRNA 沉默有两种竞争模型。一种模型假设 Regnase-1 与另一种 RNA 结合蛋白 Roquin-1 一起作用，Roquin-1 将 Regnase-1 招募到特定的 mRNA 上。另一种模型则提出这两种蛋白是分开作用的。我们通过研究 Regnase-1 的秀丽隐杆线虫同源物 REGE-1，揭示了它与 RLE-1（线虫中 Roquin-1 的对应物）之间的功能关系。虽然这两种蛋白对于 mRNA 沉默都是必需的，但 REGE-1 和 RLE-1 似乎彼此独立地与靶 mRNA 结合。因此，尽管 REGE-1/Regnase-1 和 RLE-1/Roquin-1 之间的功能相互依赖性是保守的，但潜在的机制可能表现出物种特异性的差异，为这个重要的转录后调控机制的进化提供了一个罕见的视角。
