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
State Key Laboratory of Virology and Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA.
Nat Struct Mol Biol. 2017 Oct;24(10):816-824. doi: 10.1038/nsmb.3455. Epub 2017 Aug 28.
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.
已知微小RNA（miRNA）的生物合成受多种RNA结合蛋白（RBP）调控，但在大多数情况下，单个RBP似乎仅影响一小部分靶标miRNA的加工过程。在此，我们报告RNA结合蛋白NONO-PSF异二聚体在HeLa细胞中结合大量表达的初级miRNA（pri-miRNA），从而通过Drosha-DGCR8微处理器全面增强pri-miRNA的加工过程。NONO和PSF是由长链非编码RNA（lncRNA）NEAT1组织形成的旁斑的关键组成部分。我们进一步证明，NEAT1对整体pri-miRNA加工也有深远影响。机制剖析表明，NEAT1广泛地与NONO-PSF异二聚体以及许多其他RBP相互作用，并且NEAT1中的多个RNA片段，包括其3'端附近的一个“假pri-miRNA”，有助于吸引微处理器。这些发现提示了一种“鸟巢”模型，即lncRNA在细胞核中协调潜在的一整类小非编码RNA的高效加工。
