mRNA 3′ end processing is an essential step in gene expression. It is well established that canonical eukaryotic pre-mRNA 3′ processing is carried out within a macromolecular machinery consisting of dozens of trans-acting proteins. However, it is unknown whether RNAs play any role in this process. Unexpectedly, we found that a subset of small nucleolar RNAs (snoRNAs) are associated with the mammalian mRNA 3′ processing complex. These snoRNAs primarily interact with Fip1, a component of cleavage and polyadenylation specificity factor (CPSF). We have functionally characterized one of these snoRNAs and our results demonstrated that the U/A-rich SNORD50A inhibits mRNA 3′ processing by blocking the Fip1-poly(A) site (PAS) interaction. Consistently, SNORD50A depletion altered the Fip1–RNA interaction landscape and changed the alternative polyadenylation (APA) profiles and/or transcript levels of a subset of genes. Taken together, our data revealed a novel function for snoRNAs and provided the first evidence that non-coding RNAs may play an important role in regulating mRNA 3′ processing.

中文翻译：

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snoRNA调节mRNA 3'末端加工并调节mRNA子集的表达

mRNA 3'末端加工是基因表达中必不可少的步骤。众所周知，经典的真核mRNA前3'加工是在由数十种反式作用蛋白组成的大分子机器中进行的。但是，尚不清楚RNA在此过程中是否发挥任何作用。出乎意料的是，我们发现小核仁RNA（snoRNA）的子集与哺乳动物mRNA 3'加工复合体相关。这些snoRNA主要与Fip1相互作用，Fip1是切割和聚腺苷酸特异性因子（CPSF）的组成部分。我们已经在功能上表征了这些snoRNA之一，我们的结果表明，富含U / A的SNORD50A通过阻断Fip1-poly（A）位点（PAS）相互作用来抑制mRNA 3'加工。始终如一 SNORD50A耗竭改变了Fip1-RNA相互作用的格局，并改变了一部分基因的替代多腺苷酸化（APA）谱和/或转录水平。综上所述，我们的数据揭示了snoRNA的新功能，并提供了第一个证据，即非编码RNA可能在调节mRNA 3'加工中起重要作用。