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

• DOI: 10.1016/j.molcel.2016.06.014
• Publication Date: 2016-07-16T05:29:38Z
• Authors: 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
• Keywords: Drosha; Chromatin immunoprecipitation; Dicer

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.