Institute of Plant and Microbial Biology, Academia Sinica, Taipei 115201, Taiwan.
Genenet Technology (UK) Limited, 128 City Road, London EC1V 2NX, UK.
G3 (Bethesda). 2023 Sep 30;13(10). doi: 10.1093/g3journal/jkad175.
Coilin is a scaffold protein essential for the structure of Cajal bodies, which are nucleolar-associated, nonmembranous organelles that coordinate the assembly of nuclear ribonucleoproteins (RNPs) including spliceosomal snRNPs. To study coilin function in plants, we conducted a genetic suppressor screen using a coilin (coi1) mutant in Arabidopsis thaliana and performed an immunoprecipitation-mass spectrometry analysis on coilin protein. The coi1 mutations modify alternative splicing of a GFP reporter gene, resulting in a hyper-GFP phenotype in young coi1 seedlings relative to the intermediate wild-type level. As shown here, this hyper-GFP phenotype is extinguished in older coi1 seedlings by posttranscriptional gene silencing triggered by siRNAs derived from aberrant splice variants of GFP pre-mRNA. In the coi1 suppressor screen, we identified suppressor mutations in WRAP53, a putative coilin-interacting protein; SMU2, a predicted splicing factor; and ZCH1, an incompletely characterized zinc finger protein. These suppressor mutations return the hyper-GFP fluorescence of young coi1 seedlings to the intermediate wild-type level. Additionally, coi1 zch1 mutants display more extensive GFP silencing and elevated levels of GFP siRNAs, suggesting the involvement of wild-type ZCH1 in siRNA biogenesis or stability. The immunoprecipitation-mass spectrometry analysis reinforced the roles of coilin in pre-mRNA splicing, nucleolar chromatin structure, and rRNA processing. The participation of coilin in these processes, at least some of which incorporate small RNAs, supports the hypothesis that coilin provides a chaperone for small RNA trafficking. Our study demonstrates the usefulness of the GFP splicing reporter for investigating alternative splicing, ribosome biogenesis, and siRNA-mediated silencing in the context of coilin function.
科尔林是一种支架蛋白,对 Cajal 体的结构至关重要,Cajal 体是核仁相关的非膜细胞器,协调核核糖核蛋白(RNP)的组装,包括剪接体 snRNP。为了研究科尔林在植物中的功能,我们在拟南芥中使用 coilin(coi1)突变体进行了遗传抑制筛选,并对 coilin 蛋白进行了免疫沉淀-质谱分析。coi1 突变修饰了 GFP 报告基因的可变剪接,导致 coi1 幼苗相对于中间野生型水平表现出超 GFP 表型。如这里所示,这种超 GFP 表型在较老的 coi1 幼苗中被由 GFP 前体 mRNA 异常剪接变体衍生的 siRNA 触发的转录后基因沉默所消除。在 coi1 抑制筛选中,我们在 WRAP53 中鉴定到抑制突变,WRAP53 是一种假定的 coilin 相互作用蛋白;SMU2,一种预测的剪接因子;和 ZCH1,一种不完全特征的锌指蛋白。这些抑制突变将 coi1 幼苗的超 GFP 荧光恢复到中间野生型水平。此外,coi1 zch1 突变体显示出更广泛的 GFP 沉默和 GFP siRNA 水平升高,表明野生型 ZCH1 参与 siRNA 的生物发生或稳定性。免疫沉淀-质谱分析加强了 coilin 在 pre-mRNA 剪接、核仁染色质结构和 rRNA 加工中的作用。coilin 参与这些过程,其中至少一些过程涉及小 RNA,支持 coilin 为小 RNA 运输提供伴侣的假说。我们的研究表明,GFP 剪接报告基因在 coilin 功能背景下研究可变剪接、核糖体生物发生和 siRNA 介导的沉默是有用的。