title: 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.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Haoming
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Liang
authors.affiliation: McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Rahul K
authors.initials: RK
authors.lastname: Kollipara
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsui
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Xiong
authors.initials: X
authors.lastname: Ke
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Byung-Cheon
authors.initials: BC
authors.lastname: Jeong
authors.affiliation: International Institute for Integrated Sleep Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kyoung Shin
authors.initials: KS
authors.lastname: Yoo
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Gaya P
authors.initials: GP
authors.lastname: Yadav
authors.affiliation: Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Kinch
authors.affiliation: Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Grishin
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yunsun
authors.initials: Y
authors.lastname: Nam
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Corey
authors.affiliation: McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kittler
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; International Institute for Integrated Sleep Medicine, University of Tsukuba, Tsukuba 305-8575, Japan; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: qinghua.liu@utsouthwestern.edu.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D002843:Chromatin; C474043:DGCR8 protein, human; D004268:DNA-Binding Proteins; C548039:HP1BP3 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D004257:DNA Polymerase II; C517918:DROSHA protein, human; D043244:Ribonuclease III
keywords: Drosha-DGCR8; HP1BP3; co-transcriptional processing; histone H1; pri-miRNA