A variety of dicer substrates in human and C. elegans

Cell. 2014 Nov 20;159(5):1153-1167. doi: 10.1016/j.cell.2014.10.040.

Abstract

The endoribonuclease Dicer is known for its central role in the biogenesis of eukaryotic small RNAs/microRNAs. Despite its importance, Dicer target transcripts have not been directly mapped. Here, we apply biochemical methods to human cells and C. elegans and identify thousands of Dicer-binding sites. We find known and hundreds of additional miRNAs with high sensitivity and specificity. We also report structural RNAs, promoter RNAs, and mitochondrial transcripts as Dicer targets. Interestingly, most Dicer-binding sites reside on mRNAs/lncRNAs and are not significantly processed into small RNAs. These passive sites typically harbor small, Dicer-bound hairpins within intact transcripts and generally stabilize target expression. We show that passive sites can sequester Dicer and reduce microRNA expression. mRNAs with passive sites were in human and worm significantly associated with processing-body/granule function. Together, we provide the first transcriptome-wide map of Dicer targets and suggest conserved binding modes and functions outside of the miRNA pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromatin Immunoprecipitation
  • DEAD-box RNA Helicases / metabolism*
  • Humans
  • MicroRNAs / metabolism
  • Photochemistry
  • RNA / metabolism
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / metabolism
  • RNA, Mitochondrial
  • RNA-Binding Proteins / metabolism
  • Ribonuclease III / metabolism*
  • Transcription Initiation Site
  • Transcriptome

Substances

  • Caenorhabditis elegans Proteins
  • DGCR8 protein, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Mitochondrial
  • RNA-Binding Proteins
  • RNA
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

Associated data

  • GEO/GSE55333