A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.

A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.
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DOI:
10.1016/j.cell.2018.05.022
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发表时间:
2018-07-12
期刊:
影响因子:
64.5
通讯作者:
Bartel DP
Bartel DP
中科院分区:
生物学1区
文献类型:
--
作者:
Kleaveland B;Shi CY;Stefano J;Bartel DP

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非编码RNA(ncRNA)在基因调控中发挥着越来越重要的作用。在这里,我们描述了一个以四个ncRNA为中心的调控网络-一个长ncRNA,一个环状RNA和两个microRNA-在小鼠中使用基因编辑来探测破坏该网络关键组分的分子后果。长ncRNA Cyrano使用与miR-7广泛配对的位点来触发这种microRNA的破坏。Cyrano-directed miR-7降解比之前描述的靶向microRNA降解的例子更有效,后者主要来自人工和病毒RNA的研究。通过降低miR-7水平,Cyrano阻止了miR-7靶向mRNA的抑制,并使Cdr 1as积累,Cdr 1as是一种已知调节神经元活性的环状RNA。在没有Cyrano的情况下,过量的miR-7会导致神经元中Cdr 1as的细胞质破坏,部分原因是第二种miRNA miR-671增强了Cdr 1as的切割。因此,几种类型的ncRNA可以合作建立复杂的调控网络。
Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more effective than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as in neurons, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network.
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