HP1BP3, a Chromatin Retention Factor for Co-transcriptional MicroRNA Processing

Mol Cell. 2016 Aug 4;63(3):420-32. doi: 10.1016/j.molcel.2016.06.014. Epub 2016 Jul 14.

Abstract

Recent studies suggest that the microprocessor (Drosha-DGCR8) complex can be recruited to chromatin to catalyze co-transcriptional processing of primary microRNAs (pri-miRNAs) in mammalian cells. However, the molecular mechanism of co-transcriptional miRNA processing is poorly understood. Here we find that HP1BP3, a histone H1-like chromatin protein, specifically associates with the microprocessor and promotes global miRNA biogenesis in human cells. Chromatin immunoprecipitation (ChIP) studies reveal genome-wide co-localization of HP1BP3 and Drosha and HP1BP3-dependent Drosha binding to actively transcribed miRNA loci. Moreover, HP1BP3 specifically binds endogenous pri-miRNAs and facilitates the Drosha/pri-miRNA association in vivo. Knockdown of HP1BP3 compromises pri-miRNA processing by causing premature release of pri-miRNAs from the chromatin. Taken together, these studies suggest that HP1BP3 promotes co-transcriptional miRNA processing via chromatin retention of nascent pri-miRNA transcripts. This work significantly expands the functional repertoire of the H1 family of proteins and suggests the existence of chromatin retention factors for widespread co-transcriptional miRNA processing.

Keywords: Drosha-DGCR8; HP1BP3; co-transcriptional processing; histone H1; pri-miRNA.

MeSH terms

  • Animals
  • Binding Sites
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • DNA Polymerase II / genetics
  • DNA Polymerase II / metabolism
  • DNA-Binding Proteins
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Genome, Human
  • HeLa Cells
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA Interference
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Transcription, Genetic*
  • Transfection

Substances

  • Chromatin
  • DGCR8 protein, human
  • DNA-Binding Proteins
  • HP1BP3 protein, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA-Binding Proteins
  • DNA Polymerase II
  • DROSHA protein, human
  • Ribonuclease III