title: KDM5 lysine demethylases are involved in maintenance of 3'UTR length.
abstract: The complexity by which cells regulate gene and protein expression is multifaceted and intricate. Regulation of 3' untranslated region (UTR) processing of mRNA has been shown to play a critical role in development and disease. However, the process by which cells select alternative mRNA forms is not well understood. We discovered that theSaccharomyces cerevisiaelysine demethylase, Jhd2 (also known as KDM5), recruits 3'UTR processing machinery and promotes alteration of 3'UTR length for some genes in a demethylase-dependent manner. Interaction of Jhd2 with both chromatin and RNA suggests that Jhd2 affects selection of polyadenylation sites through a transcription-coupled mechanism. Furthermore, its mammalian homolog KDM5B (also known as JARID1B or PLU1), but not KDM5A (also known as JARID1A or RBP2), promotes shortening ofCCND1transcript in breast cancer cells. Consistent with these results, KDM5B expression correlates with shortenedCCND1in human breast tumor tissues. In contrast, both KDM5A and KDM5B are involved in the lengthening ofDICER1. Our findings suggest both a novel role for this family of demethylases and a novel targetable mechanism for 3'UTR processing.
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Blair
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Zongzhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ramon Lorenzo D
authors.initials: RL
authors.lastname: Labitigan
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Lizhen
authors.identifier: 0000-0002-0452-2602
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Dinghai
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Division of Biostatistics, Dan L Duncan Comprehensive Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Zheng
authors.identifier: 0000-0003-3364-8324
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Pearson
authors.affiliation: Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Fathima I
authors.initials: FI
authors.lastname: Nazeer
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sabine M
authors.identifier: 0000-0002-6486-5287
authors.initials: SM
authors.lastname: Lang
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Rachel J
authors.identifier: 0000-0002-5700-8885
authors.initials: RJ
authors.lastname: Rines
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72032, USA.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Mackintosh
authors.affiliation: Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Moore
authors.affiliation: Division of Biostatistics, Dan L Duncan Comprehensive Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72032, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Tackett
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Qin
authors.identifier: 0000-0003-4077-453X
authors.initials: Q
authors.lastname: Yan
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056485:Retinoblastoma-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C530104:CCND1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D019938:Cyclin D1; C519119:JHD2 protein, S cerevisiae; D056484:Jumonji Domain-Containing Histone Demethylases; C070050:KDM5A protein, human; C119611:KDM5B protein, human; D056485:Retinoblastoma-Binding Protein 2; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: CCND1; DICER1; JARID1; Jhd2; KDM5; KDM5A; KDM5B; KDM5C; Lysine demethylase 5; alternative polyadenylation