Srsf10 and the minor spliceosome control tissue-specific and dynamic SR protein expression
Srsf10 and the minor spliceosome control tissue-specific and dynamic SR protein expression
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DOI：
10.7554/elife.56075
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发表时间：
2020-04-27
期刊：
影响因子：
7.7
通讯作者：
Heyd, Florian
中科院分区：
文献类型：
--
作者：
Meinke, Stefan;Goldammer, Gesine;Heyd, Florian
次要剪接体和主要剪接体控制不同内含子类型的剪接，并且被认为在很大程度上彼此独立地起作用。SR蛋白是主要与剪接体相连的剪接调节蛋白。在这里，我们表明，Srsf 10的表达是通过一个自动调节的小内含子，密切相关的Srsf 10与小剪接体丰度在不同的组织和分化阶段的哺乳动物。令人惊讶的是，所有其他SR蛋白也与次要剪接体和Srsf 10相关，并且通过Crispr/Cas9介导的自动调节外显子缺失来消除Srsf 10自动调节会诱导人类细胞系中所有SR蛋白的表达。因此，我们的数据揭示了广泛的串扰和主要内含子剪接的次要剪接体的全球影响。
Minor and major spliceosomes control splicing of distinct intron types and are thought to act largely independent of one another. SR proteins are essential splicing regulators mostly connected to the major spliceosome. Here, we show that Srsf10 expression is controlled through an autoregulated minor intron, tightly correlating Srsf10 with minor spliceosome abundance across different tissues and differentiation stages in mammals. Surprisingly, all other SR proteins also correlate with the minor spliceosome and Srsf10, and abolishing Srsf10 autoregulation by Crispr/Cas9-mediated deletion of the autoregulatory exon induces expression of all SR proteins in a human cell line. Our data thus reveal extensive crosstalk and a global impact of the minor spliceosome on major intron splicing.