School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
The John Curtin School of Medical Research, The Australian National University, Canberra 2601, Australia.
Nucleic Acids Res. 2024 Aug 27;52(15):9174-9192. doi: 10.1093/nar/gkae463.
The Cajal body, a nuclear condensate, is crucial for ribonucleoprotein assembly, including small nuclear RNPs (snRNPs). While Coilin has been identified as an integral component of Cajal bodies, its exact function remains unclear. Moreover, no Coilin ortholog has been found in unicellular organisms to date. This study unveils Mug174 (Meiosis-upregulated gene 174) as the Coilin ortholog in the fission yeast Schizosaccharomyces pombe. Mug174 forms phase-separated condensates in vitro and is often associated with the nucleolus and the cleavage body in vivo. The generation of Mug174 foci relies on the trimethylguanosine (TMG) synthase Tgs1. Moreover, Mug174 interacts with Tgs1 and U snRNAs. Deletion of the mug174+ gene in S. pombe causes diverse pleiotropic phenotypes, encompassing defects in vegetative growth, meiosis, pre-mRNA splicing, TMG capping of U snRNAs, and chromosome segregation. In addition, we identified weak homology between Mug174 and human Coilin. Notably, human Coilin expressed in fission yeast colocalizes with Mug174. Critically, Mug174 is indispensable for the maintenance of and transition from cellular quiescence. These findings highlight the Coilin ortholog in fission yeast and suggest that the Cajal body is implicated in cellular quiescence, thereby preventing human diseases.
Cajal 体是一种核凝聚物,对于核糖核蛋白组装至关重要,包括小核 RNP(snRNP)。虽然已经确定 Coilin 是 Cajal 体的一个组成部分,但它的确切功能仍不清楚。此外,迄今为止,在单细胞生物中尚未发现 Coilin 的同源物。本研究揭示了裂殖酵母 Schizosaccharomyces pombe 中的 Mug174(减数分裂上调基因 174)是 Coilin 的同源物。Mug174 在体外形成相分离凝聚物,并且在体内通常与核仁与分裂体相关联。Mug174 焦点的生成依赖于三甲基鸟苷(TMG)合酶 Tgs1。此外,Mug174 与 Tgs1 和 U snRNA 相互作用。裂殖酵母 S. pombe 中 mug174+基因的缺失会导致多种表型缺陷,包括营养生长、减数分裂、前体 mRNA 剪接、U snRNA 的 TMG 加帽以及染色体分离缺陷。此外,我们在 Mug174 与人类 Coilin 之间发现了微弱的同源性。值得注意的是,在裂殖酵母中表达的人类 Coilin 与 Mug174 共定位。至关重要的是,Mug174 对于细胞静止的维持和过渡是不可或缺的。这些发现突出了裂殖酵母中的 Coilin 同源物,并表明 Cajal 体与细胞静止有关,从而预防了人类疾病。