Nuclear Pre-snRNA Export Is an Essential Quality Assurance Mechanism for Functional Spliceosomes
Nuclear Pre-snRNA Export Is an Essential Quality Assurance Mechanism for Functional Spliceosomes
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DOI：
10.1016/j.celrep.2019.05.031
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发表时间：
2019-06-11
期刊：
影响因子：
8.8
通讯作者：
Krebber, Heike
中科院分区：
文献类型：
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作者：
Becker, Daniel;Hirsch, Anna Greta;Krebber, Heike
从前体mRNA中去除内含子是真核基因表达的重要步骤，由含有snRNA作为关键组分的剪接体介导。虽然snRNA在细胞核中转录并在同一区室中发挥作用，但除U6外，所有snRNA都穿梭于细胞质。令人惊讶的是，穿梭的生理相关性尚不清楚，特别是因为据报道酿酒酵母中的snRNA保持核。在这里，我们表明，所有的酵母前snRNAs，包括U6经历了一个逐步成熟的过程后，核出口的Mex 67和Xpo 1。Sm-和Lsm-环附着发生在细胞质中，并且对于由Cse 1和Mtr 10介导的snRNA再输入是重要的。最后，核前体snRNA切割和5 '帽的三甲基化完成穿梭。重要的是，阻止前体snRNA被输出或加工会导致错误的剪接体组装和随后的全基因组剪接缺陷。因此，前体snRNA输出对于功能性剪接是必需的，并且类似于进化上保守的质量保证步骤。
Removal of introns from pre-mRNAs is an essential step in eukaryotic gene expression, mediated by spliceosomes that contain snRNAs as key components. Although snRNAs are transcribed in the nucleus and function in the same compartment, all except U6 shuttle to the cytoplasm. Surprisingly, the physiological relevance for shuttling is unclear, in particular because the snRNAs in Saccharomyces cerevisiae were reported to remain nuclear. Here, we show that all yeast pre-snRNAs including U6 undergo a stepwise maturation process after nuclear export by Mex67 and Xpo1. Sm-and Lsm-ring attachment occurs in the cytoplasm and is important for the snRNA re-import, mediated by Cse1 and Mtr10. Finally, nuclear pre-snRNA cleavage and trimethylation of the 5'-cap finalizes shuttling. Importantly, preventing pre-snRNAs from being exported or processed results in faulty spliceosome assembly and subsequent genome-wide splicing defects. Thus, pre-snRNA export is obligatory for functional splicing and resembles an essential evolutionarily conserved quality assurance step.