Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Nat Struct Mol Biol. 2010 Apr;17(4):403-9. doi: 10.1038/nsmb.1783. Epub 2010 Mar 28.
Spliceosomal small nuclear ribonucleoproteins (snRNPs), comprised of small nuclear RNAs (snRNAs) in complex with snRNP-specific proteins, are essential for pre-mRNA splicing. Coilin is not a snRNP protein but concentrates snRNPs and their assembly intermediates in Cajal bodies (CBs). Here we show that depletion of coilin in zebrafish embryos leads to CB dispersal, deficits in snRNP biogenesis and expression of spliced mRNA, as well as reduced cell proliferation followed by developmental arrest. Notably, injection of purified mature human snRNPs restored mRNA expression and viability. snRNAs were necessary but not sufficient for rescue, showing that only assembled snRNPs can bypass the requirement for coilin. Thus, coilin's essential function in embryos is to promote macromolecular assembly of snRNPs, likely by concentrating snRNP components in CBs to overcome rate-limiting assembly steps.
剪接体小核核糖核蛋白（snRNPs）由小核 RNA（snRNAs）与 snRNP 特异性蛋白组成，对前体 mRNA 的剪接至关重要。Coilin 不是 snRNP 蛋白，但可将 snRNPs 及其组装中间体集中在 Cajal 体（CBs）中。本文作者发现，斑马鱼胚胎中 coilin 的缺失会导致 CB 弥散、snRNP 生物发生和剪接 mRNA 的表达缺陷，以及细胞增殖减少，从而导致发育停滞。值得注意的是，注射纯化的成熟人 snRNPs 可恢复 mRNA 表达和活力。snRNAs 是必需的，但不是充分的拯救条件，这表明只有组装好的 snRNPs 才能绕过 coilin 的需求。因此，coilin 在胚胎中的必需功能是促进 snRNPs 的大分子组装，可能是通过将 snRNP 成分集中在 CB 中，以克服限速组装步骤。
