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

Haoming Liu, Chunyang Liang, Rahul K. Kollipara, Masayuki Matsui, Xiong Ke, Byung Cheon Jeong, Zhiqiang Wang, Kyoung Shin Yoo, Gaya P. Yadav, Lisa N. Kinch, Nicholas V. Grishin, Yunsun Nam, David R. Corey, Ralf Kittler, Qinghua Liu

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)420-432
Number of pages13
JournalMolecular cell
Volume63
Issue number3
DOIs
StatePublished - Aug 4 2016

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Keywords

  • Drosha-DGCR8
  • HP1BP3
  • co-transcriptional processing
  • histone H1
  • pri-miRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Liu, H., Liang, C., Kollipara, R. K., Matsui, M., Ke, X., Jeong, B. C., Wang, Z., Yoo, K. S., Yadav, G. P., Kinch, L. N., Grishin, N. V., Nam, Y., Corey, D. R., Kittler, R., & Liu, Q. (2016). HP1BP3, a Chromatin Retention Factor for Co-transcriptional MicroRNA Processing. Molecular cell, 63(3), 420-432. https://doi.org/10.1016/j.molcel.2016.06.014