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Sci Adv. 2016 Nov 18;2(11):e1501662. doi: 10.1126/sciadv.1501662. eCollection 2016 Nov.

KDM5 lysine demethylases are involved in maintenance of 3'UTR length.

Author information

1
Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
2
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
3
Division of Biostatistics, Dan L Duncan Comprehensive Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
4
Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
5
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72032, USA.

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 the Saccharomyces cerevisiae lysine 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 of CCND1 transcript in breast cancer cells. Consistent with these results, KDM5B expression correlates with shortened CCND1 in human breast tumor tissues. In contrast, both KDM5A and KDM5B are involved in the lengthening of DICER1. Our findings suggest both a novel role for this family of demethylases and a novel targetable mechanism for 3'UTR processing.

KEYWORDS:

CCND1; DICER1; JARID1; Jhd2; KDM5; KDM5A; KDM5B; KDM5C; Lysine demethylase 5; alternative polyadenylation

PMID:
28138513
PMCID:
PMC5262454
DOI:
10.1126/sciadv.1501662
[Indexed for MEDLINE]
Free PMC Article

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