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

Haoming Liu1, Chunyang Liang1, Rahul K Kollipara2

  • 1Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Molecular Cell
|July 19, 2016
PubMed

Insights

HP1BP3, a chromatin protein, binds pri-microRNAs (pri-miRNAs) and the microprocessor complex, promoting co-transcriptional miRNA processing by retaining transcripts on chromatin.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • MicroRNA (miRNA) biogenesis involves microprocessor complex processing of primary miRNAs (pri-miRNAs).
  • Co-transcriptional miRNA processing, where pri-miRNA processing occurs during transcription, is a recently suggested mechanism.
  • The precise molecular mechanisms governing co-transcriptional miRNA processing remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanism of co-transcriptional miRNA processing.
  • To identify proteins involved in the recruitment and function of the microprocessor complex at miRNA genes.
  • To investigate the role of chromatin proteins in regulating miRNA biogenesis.

Main Methods:

  • Chromatin immunoprecipitation (ChIP) to assess protein-DNA and protein-protein interactions at miRNA loci.
  • Co-immunoprecipitation to study protein complex formation in vivo.
  • RNA immunoprecipitation (RIP) to detect RNA binding proteins.
  • HP1BP3 knockdown experiments to evaluate its functional impact on miRNA processing.

Main Results:

  • HP1BP3, a histone H1-like protein, specifically associates with the microprocessor complex (Drosha-DGCR8).
  • Genome-wide ChIP analysis revealed co-localization of HP1BP3 and Drosha at actively transcribed miRNA loci.
  • HP1BP3 directly binds pri-miRNAs and facilitates Drosha binding, promoting pri-miRNA processing.
  • HP1BP3 knockdown leads to premature release of pri-miRNAs from chromatin, impairing miRNA biogenesis.

Conclusions:

  • HP1BP3 acts as a chromatin retention factor for nascent pri-miRNA transcripts.
  • HP1BP3 promotes co-transcriptional miRNA processing by facilitating microprocessor complex function at miRNA genes.
  • This study reveals a novel role for HP1BP3 in miRNA biogenesis and expands the known functions of the H1 protein family.
Keywords:
Drosha-DGCR8HP1BP3co-transcriptional processinghistone H1pri-miRNA

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