NEAT1 scaffolds RNA-binding proteins and the Microprocessor to globally enhance pri-miRNA processing.

NEAT1 scaffolds RNA-binding proteins and the Microprocessor to globally enhance pri-miRNA processing.
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DOI:
10.1038/nsmb.3455
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发表时间:
2017-10
影响因子:
16.8
通讯作者:
Fu XD
Fu XD
中科院分区:
生物学1区
文献类型:
--
作者:
Jiang L;Shao C;Wu QJ;Chen G;Zhou J;Yang B;Li H;Gou LT;Zhang Y;Wang Y;Yeo GW;Zhou Y;Fu XD

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MicroRNA biogenesis is known to be modulated by a variety of RNA binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. We herein report that the RNA binding NONO/PSF heterodimer binds a large number of expressed pri-miRNAs in HeLa cells to globally enhance pri-miRNA processing by the Drosha/DGCR8 Microprocessor. Because NONO/PSF are key components of paraspeckles organized by the lncRNA NEAT1, we further demonstrate that NEAT1 also has a profound effect on global pri-miRNA processing. Mechanistic dissection reveals that NEAT1 broadly interacts with NONO/PSF as well as many other RBPs, and that multiple RNA segments in NEAT1, including a “pseudo pri-miRNA” near its 3′ end, help attract the Microprocessor. These findings suggest a bird nest model for a large non-coding RNA to orchestrate efficient processing of almost an entire class of small non-coding RNAs in the nucleus.
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