Poly(A)-specific ribonuclease sculpts the 3′ ends of microRNAs
Poly(A)-specific ribonuclease sculpts the 3′ ends of microRNAs
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DOI：
10.1261/rna.069633.118
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发表时间：
2019-03-01
期刊：
影响因子：
4.5
通讯作者：
Shin, Chanseok
中科院分区：
文献类型：
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作者：
Lee, Dooyoung;Park, Daechan;Shin, Chanseok
后生动物microRNA（miRNAs）的3 '末端最初在成熟过程中由RNase III酶限定，但随后经历几种酶活性的广泛修饰。例如，末端核苷酸转移酶（TENT）通过向其3 '末端添加一个或几个核苷酸来延长miRNA，这偶尔导致miRNA稳定性或功能的差异调节。然而，缩短miRNA的催化实体和这种缩短的分子后果还不太清楚，特别是在脊椎动物中。在这里，我们报道了poly（A）-specific ribonuclease（PARN）在人类细胞中雕刻miRNAs的3 '末端。通过产生PARN敲除细胞并表征它们的miRNAome，我们证明PARN使来自基因组或通过TENT连接的miRNAs的3 '延伸延长，从而有效地减少miRNAs的长度。令人惊讶的是，PARN介导的缩短对miRNA的稳定性几乎没有影响，这表明该过程可能是为了完成miRNA的成熟，而不是启动miRNA的衰变。PARN介导的缩短在大多数miRNA中普遍存在，并且似乎是有助于脊椎动物miRNA的3 '端形成的保守机制。我们的发现将miRNAs添加到了3 '端形成依赖于PARN的非编码RNA的扩展列表中。
The 3' ends of metazoan microRNAs (miRNAs) are initially defined by the RNase III enzymes during maturation, but subsequently experience extensive modifications by several enzymatic activities. For example, terminal nucleotidyltransferases (TENTs) elongate miRNAs by adding one or a few nucleotides to their 3' ends, which occasionally leads to differential regulation of miRNA stability or function. However, the catalytic entities that shorten miRNAs and the molecular consequences of such shortening are less well understood, especially in vertebrates. Here, we report that poly(A)-specific ribonuclease (PARN) sculpts the 3' ends of miRNAs in human cells. By generating PARN knockout cells and characterizing their miRNAome, we demonstrate that PARN digests the 3' extensions of miRNAs that are derived from the genome or attached by TENTs, thereby effectively reducing the length of miRNAs. Surprisingly, PARN-mediated shortening has little impact on miRNA stability, suggesting that this process likely operates to finalize miRNA maturation, rather than to initiate miRNA decay. PARN-mediated shortening is pervasive across most miRNAs and appears to be a conserved mechanism contributing to the 3' end formation of vertebrate miRNAs. Our findings add miRNAs to the expanding list of noncoding RNAs whose 3' end formation depends on PARN.