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

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.

DOI: 10.1016/j.molcel.2016.06.014

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Cite this paper

@article{Liu2016HP1BP3AC, title={HP1BP3, a Chromatin Retention Factor for Co-transcriptional MicroRNA Processing.}, author={Haoming Liu and Chunyang Liang and Rahul K. Kollipara and Masayuki Matsui and Xiong Ke and Byung-Cheon Jeong and Zhiqiang Wang and Kyoung Shin Yoo and Gaya Prasad Yadav and Lisa N. Kinch and Nicholas V Grishin and Yunsun Nam and David R. Corey and Ralf Kittler and Qinghua Liu}, journal={Molecular cell}, year={2016}, volume={63 3}, pages={420-32} }