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

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

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.

MeSH terms

  • DNA-Binding Proteins
  • HeLa Cells
  • Humans
  • MicroRNAs / metabolism*
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Octamer Transcription Factors / metabolism*
  • PTB-Associated Splicing Factor / metabolism*
  • Protein Binding
  • RNA Processing, Post-Transcriptional*
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III / metabolism*

Substances

  • DGCR8 protein, human
  • DNA-Binding Proteins
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • NONO protein, human
  • Nuclear Matrix-Associated Proteins
  • Octamer Transcription Factors
  • PTB-Associated Splicing Factor
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • DROSHA protein, human
  • Ribonuclease III