A snoRNA modulates mRNA 3' end processing and regulates the expression of a subset of mRNAs.

A snoRNA modulates mRNA 3' end processing and regulates the expression of a subset of mRNAs.
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DOI:
10.1093/nar/gkx651
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发表时间:
2017-09-06
影响因子:
14.9
通讯作者:
Yao C
Yao C
中科院分区:
生物学2区
文献类型:
--
作者:
Huang C;Shi J;Guo Y;Huang W;Huang S;Ming S;Wu X;Zhang R;Ding J;Zhao W;Jia J;Huang X;Xiang AP;Shi Y;Yao C

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mRNA 3′末端加工是基因表达的重要步骤。经典的真核生物前mRNA 3′端加工是在一个由几十种反式作用蛋白组成的大分子机器中进行的。然而,目前尚不清楚RNA是否在这一过程中发挥作用。出乎意料的是,我们发现一个小核仁RNA(snoRNA)的子集与哺乳动物的mRNA 3′加工复合物。这些snoRNA主要与Fip 1相互作用,Fip 1是切割和多聚腺苷酸化特异性因子(CPSF)的一个成分。我们对其中一种snoRNA进行了功能表征,结果表明富含U/A的SNORD 50 A通过阻断Fip 1-poly(A)site(PAS)相互作用抑制mRNA 3′加工。同样,SNORD 50 A缺失改变了Fip 1-RNA相互作用的景观,并改变了替代聚腺苷酸化(阿帕)概况和/或转录水平的一个子集的基因。总之,我们的数据揭示了snoRNA的一种新功能,并首次证明非编码RNA可能在调节mRNA 3′加工中起重要作用。
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.
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