1. KDM5 lysine demethylases are involved in maintenance of 3'UTR length.
- Author
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Blair LP, Liu Z, Labitigan RL, Wu L, Zheng D, Xia Z, Pearson EL, Nazeer FI, Cao J, Lang SM, Rines RJ, Mackintosh SG, Moore CL, Li W, Tian B, Tackett AJ, and Yan Q
- Subjects
- Breast Neoplasms genetics, Cyclin D1 genetics, Cyclin D1 metabolism, DEAD-box RNA Helicases genetics, DEAD-box RNA Helicases metabolism, Female, Humans, Jumonji Domain-Containing Histone Demethylases genetics, MCF-7 Cells, Neoplasm Proteins genetics, Nuclear Proteins genetics, Repressor Proteins genetics, Retinoblastoma-Binding Protein 2 genetics, Retinoblastoma-Binding Protein 2 metabolism, Ribonuclease III genetics, Ribonuclease III metabolism, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, 3' Untranslated Regions, Breast Neoplasms enzymology, Jumonji Domain-Containing Histone Demethylases metabolism, Neoplasm Proteins metabolism, Nuclear Proteins metabolism, Repressor Proteins metabolism
- 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.
- Published
- 2016
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