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.  Mol. Cell 63(3): 420--432.

FBrf0250765

Research paper

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.

PMC4975613 (PMC) (EuropePMC)