Primary RNA transcripts are processed in a plethora of ways to become mature functional forms. In one example, human spliceosomal U snRNAs are matured at their 3′‐end by an exonuclease termed TOE1. This process is important because mutations in TOE1 gene can cause a human genetic disease, pontocerebellar hypoplasia (PCH). Nevertheless, TOE1 may not be the only maturation exonuclease for U snRNAs in the cell. Here, we biochemically identify two exonucleolytic factors, Interferon‐stimulated gene 20‐kDa protein (ISG20) and the nuclear exosome as such candidates, using a newly developed in vitro system that recapitulates 3′‐end maturation of U1 snRNA. However, extensive 3′‐end sequencing of endogenous U1 snRNA of the knockdown (KD) cells revealed that these factors are not the maturation factors per se. Instead, the nascent transcripts of the spliceosomal U snRNAs as well as of unstable U1 variants were found to increase in quantity upon KD of the factors. These results indicated that ISG20 and the nuclear exosome promote the degradation of nascent spliceosomal U snRNAs and U1 variants, and therefore implied their role in the quality control of newly synthesized U snRNAs.

中文翻译：

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ISG20和核外泌体促进剪接的U snRNA和U1变体的新生转录本不稳定

初级RNA转录物以多种方式加工成成熟的功能形式。在一个例子中，人类剪接体U snRNA在其3'端被称为TOE1的核酸外切酶成熟。这个过程很重要，因为TOE1基因中的突变可以导致人类​​遗传疾病，小脑发育不全（PCH）。尽管如此，TOE1可能不是细胞中U snRNA的唯一成熟核酸外切酶。在这里，我们使用新开发的体外系统概括了U1 snRNA的3'端成熟，通过生化方法鉴定了两种外切核酸因子，即干扰素刺激的基因20-kDa蛋白（ISG20）和核外泌体。但是，对敲低（KD）细胞的内源性U1 snRNA进行广泛的3'端测序，发现这些因素本身并不是成熟因素。取而代之的是，发现剪接体U snRNA的初生转录本以及不稳定的U1变体在KD因子增加时数量增加。这些结果表明，ISG20和核外泌体可促进新生剪接体U snRNA和U1变体的降解，