Evidence for a cytoplasmic microprocessor of pri-miRNAs
Evidence for a cytoplasmic microprocessor of pri-miRNAs
复制标题
DOI：
10.1261/rna.032268.112
复制
发表时间：
2012-07-01
期刊：
影响因子：
4.5
通讯作者：
Tenoever, Benjamin R.
中科院分区：
文献类型：
--
作者：
Shapiro, Jillian S.;Langlois, Ryan A.;Tenoever, Benjamin R.
MicroRNAs(MiRNAs)是一类非编码RNA，通过转录后沉默来微调基因的表达。虽然miRNA的生物发生是由核微处理器以循序渐进的方式进行的，但也发现了罕见的非规范miRNAs。在这里，我们描述了与病毒来源的细胞质初级miRNAs(c-pri-miRNAs)的处理相关的分子成分和独特的属性。RNA原位杂交和细胞分裂抑制表明c-pri-miRNA裂解完全没有核参与，而遗传学研究表明成熟仍然依赖于典型的核RNaseIII酶DROSHA。DROSHA的参与是通过在病毒感染后戏剧性地重新定位到细胞质而介导的。深入的测序分析表明，DROSHA的细胞质定位不会影响感染期间的内源miRNA格局，尽管允许在细胞质中强劲地合成病毒衍生的miRNAs。综上所述，这项研究描述了DROSHA在病毒感染背景下处理高结构细胞质RNA中的独特功能。
microRNAs (miRNAs) represent a class of noncoding RNAs that fine-tune gene expression through post-transcriptional silencing. While miRNA biogenesis occurs in a stepwise fashion, initiated by the nuclear microprocessor, rare noncanonical miRNAs have also been identified. Here we characterize the molecular components and unique attributes associated with the processing of virus-derived cytoplasmic primary miRNAs (c-pri-miRNAs). RNA in situ hybridization and inhibition of cellular division demonstrated a complete lack of nuclear involvement in c-pri-miRNA cleavage while genetic studies revealed that maturation still relied on the canonical nuclear RNase III enzyme, Drosha. The involvement of Drosha was mediated by a dramatic relocalization to the cytoplasm following virus infection. Deep sequencing analyses revealed that the cytoplasmic localization of Drosha does not impact the endogenous miRNA landscape during infection, despite allowing for robust synthesis of virus-derived miRNAs in the cytoplasm. Taken together, this research describes a unique function for Drosha in the processing of highly structured cytoplasmic RNAs in the context of virus infection.