A Human snoRNA With microRNA-like Functions

Mol Cell. 2008 Nov 21;32(4):519-28. doi: 10.1016/j.molcel.2008.10.017.

Abstract

Small noncoding RNAs function in concert with Argonaute (Ago) proteins to regulate gene expression at the level of transcription, mRNA stability, or translation. Ago proteins bind small RNAs and form the core of silencing complexes. Here, we report the analysis of small RNAs associated with human Ago1 and Ago2 revealed by immunoprecipitation and deep sequencing. Among the reads, we find small RNAs originating from the small nucleolar RNA (snoRNA) ACA45. Moreover, processing of ACA45 requires Dicer activity but is independent of Drosha/DGCR8. Using bioinformatic prediction algorithms and luciferase reporter assays, we uncover the mediator subunit CDC2L6 as one potential mRNA target of ACA45 small RNAs, suggesting a role for ACA45-processing products in posttranscriptional gene silencing. We further identify a number of human snoRNAs with microRNA (miRNA)-like processing signatures. We have, therefore, identified a class of small RNAs in human cells that originate from snoRNAs and can function like miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Argonaute Proteins
  • Cell Line
  • Computational Biology / methods
  • DEAD-box RNA Helicases / metabolism
  • Endoribonucleases / metabolism
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factors / metabolism
  • Genes, Reporter
  • Humans
  • Kidney / cytology
  • Luciferases / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Models, Biological
  • RNA Interference
  • RNA Processing, Post-Transcriptional
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism*
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism
  • Ribonuclease III

Substances

  • AGO1 protein, human
  • AGO2 protein, human
  • Argonaute Proteins
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factors
  • MicroRNAs
  • RNA, Small Interfering
  • RNA, Small Nucleolar
  • RNA-Induced Silencing Complex
  • Luciferases
  • Endoribonucleases
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases