Polymerases and exonucleases act on 3′ ends of nascent RNAs to promote their maturation or degradation but how the balance between these activities is controlled to dictate the fates of cellular RNAs remains poorly understood. Here, we identify a central role for the human DEDD deadenylase TOE1 in distinguishing the fates of small nuclear (sn)RNAs of the spliceosome from unstable genome-encoded snRNA variants. We found that TOE1 promotes maturation of all regular RNA polymerase II transcribed snRNAs of the major and minor spliceosomes by removing posttranscriptional oligo(A) tails, trimming 3′ ends, and preventing nuclear exosome targeting. In contrast, TOE1 promotes little to no maturation of tested U1 variant snRNAs, which are instead targeted by the nuclear exosome. These observations suggest that TOE1 is positioned at the center of a 3′ end quality control pathway that selectively promotes maturation and stability of regular snRNAs while leaving snRNA variants unprocessed and exposed to degradation in what could be a widespread mechanism of RNA quality control given the large number of noncoding RNAs processed by DEDD deadenylases.

中文翻译：

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成熟和降解之间的竞争驱动人类 snRNA 3' 末端质量控制。

聚合酶和核酸外切酶作用于新生 RNA 的 3' 末端以促进其成熟或降解，但如何控制这些活动之间的平衡以决定细胞 RNA 的命运仍然知之甚少。在这里，我们确定了人类 DEDD 脱腺苷酸酶 TOE1 在区分剪接体的小核 (sn) RNA 与不稳定的基因组编码的 snRNA 变体的命运方面的核心作用。我们发现 TOE1 通过去除转录后 oligo(A) 尾部、修剪 3' 末端和防止核外泌体靶向来促进主要和次要剪接体的所有常规 RNA 聚合酶 II 转录的 snRNA 的成熟。相比之下，TOE1 几乎不促进测试的 U1 变体 snRNA 的成熟，而是由核外泌体靶向。