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Nat Struct Mol Biol. 2017 Oct;24(10):816-824. doi: 10.1038/nsmb.3455. Epub 2017 Aug 28.

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

Author information

1
State Key Laboratory of Virology and Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
2
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA.
3
Institute of Molecular Medicine, Peking University, Beijing, China.
4
Institute for Advanced Studies, Wuhan University, Wuhan, China.
5
Institute of Genomic Medicine, University of California, San Diego, La Jolla, California, USA.

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.

PMID:
28846091
PMCID:
PMC5766049
DOI:
10.1038/nsmb.3455
[Indexed for MEDLINE]
Free PMC Article

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