Regulation of pri-miRNA processing by a long noncoding RNA transcribed from an ultraconserved region

Mol Cell. 2014 Jul 3;55(1):138-47. doi: 10.1016/j.molcel.2014.05.005. Epub 2014 Jun 5.


Noncoding RNAs (ncRNAs) control cellular programs by affecting protein-coding genes, but evidence increasingly points to their involvement in a network of ncRNA-ncRNA interactions. Here, we show that a long ncRNA, Uc.283+A, controls pri-miRNA processing. Regulation requires complementarity between the lower stem region of the pri-miR-195 transcript and an ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In addition to identifying a case of RNA-directed regulation of miRNA biogenesis, our study reveals regulatory networks involving different ncRNA classes of importance in cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Conserved Sequence
  • HCT116 Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Processing, Post-Transcriptional
  • RNA, Long Noncoding / metabolism
  • RNA, Long Noncoding / physiology*


  • MIRN195 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding

Associated data

  • GEO/GSE56841