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

  • Author(s): Jiang, Li;
  • Shao, Changwei;
  • Wu, Qi-Jia;
  • Chen, Geng;
  • Zhou, Jie;
  • Yang, Bo;
  • Li, Hairi;
  • Gou, Lan-Tao;
  • Zhang, Yi;
  • Wang, Yangming;
  • Yeo, Gene W;
  • Zhou, Yu;
  • Fu, Xiang-Dong
  • et al.

Published Web Location

https://doi.org/10.1038/nsmb.3455
Abstract

MicroRNA (miRNA) 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. Here, we 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. NONO and PSF are key components of paraspeckles organized by the long noncoding RNA (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 the NONO-PSF heterodimer 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 in which an lncRNA orchestrates efficient processing of potentially an entire class of small noncoding RNAs in the nucleus.

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