KDM5 lysine demethylases are involved in maintenance of 3′UTR length

Lauren P. Blair, Zongzhi Liu, Ramon Lorenzo D. Labitigan, Lizhen Wu, Dinghai Zheng, Zheng Xia, Erica L. Pearson, Fathima I. Nazeer, Jian Cao, Sabine M. Lang, Rachel J. Rines, Samuel G. Mackintosh, Claire L. Moore, Wei Li, Bin Tian, Alan J. Tackett, Qin Yan

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere1501662
JournalScience Advances
Volume2
Issue number11
DOIs
StatePublished - Nov 1 2016

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Lysine
Maintenance
Breast Neoplasms
Messenger RNA
Polyadenylation
3' Untranslated Regions
Chromatin
Saccharomyces cerevisiae
RNA
Gene Expression
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Blair, L. P., Liu, Z., Labitigan, R. L. D., Wu, L., Zheng, D., Xia, Z., ... Yan, Q. (2016). KDM5 lysine demethylases are involved in maintenance of 3′UTR length. Science Advances, 2(11), [e1501662]. https://doi.org/10.1126/sciadv.1501662
Blair, Lauren P. ; Liu, Zongzhi ; Labitigan, Ramon Lorenzo D. ; Wu, Lizhen ; Zheng, Dinghai ; Xia, Zheng ; Pearson, Erica L. ; Nazeer, Fathima I. ; Cao, Jian ; Lang, Sabine M. ; Rines, Rachel J. ; Mackintosh, Samuel G. ; Moore, Claire L. ; Li, Wei ; Tian, Bin ; Tackett, Alan J. ; Yan, Qin. / KDM5 lysine demethylases are involved in maintenance of 3′UTR length. In: Science Advances. 2016 ; Vol. 2, No. 11.
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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.",
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Blair, LP, Liu, Z, Labitigan, RLD, 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 & Yan, Q 2016, 'KDM5 lysine demethylases are involved in maintenance of 3′UTR length', Science Advances, vol. 2, no. 11, e1501662. https://doi.org/10.1126/sciadv.1501662

KDM5 lysine demethylases are involved in maintenance of 3′UTR length. / Blair, Lauren P.; Liu, Zongzhi; Labitigan, Ramon Lorenzo D.; Wu, Lizhen; Zheng, Dinghai; Xia, Zheng; Pearson, Erica L.; Nazeer, Fathima I.; Cao, Jian; Lang, Sabine M.; Rines, Rachel J.; Mackintosh, Samuel G.; Moore, Claire L.; Li, Wei; Tian, Bin; Tackett, Alan J.; Yan, Qin.

In: Science Advances, Vol. 2, No. 11, e1501662, 01.11.2016.

Research output: Contribution to journalArticle

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AU - Blair, Lauren P.

AU - Liu, Zongzhi

AU - Labitigan, Ramon Lorenzo D.

AU - Wu, Lizhen

AU - Zheng, Dinghai

AU - Xia, Zheng

AU - Pearson, Erica L.

AU - Nazeer, Fathima I.

AU - Cao, Jian

AU - Lang, Sabine M.

AU - Rines, Rachel J.

AU - Mackintosh, Samuel G.

AU - Moore, Claire L.

AU - Li, Wei

AU - Tian, Bin

AU - Tackett, Alan J.

AU - Yan, Qin

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N2 - 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.

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Blair LP, Liu Z, Labitigan RLD, Wu L, Zheng D, Xia Z et al. KDM5 lysine demethylases are involved in maintenance of 3′UTR length. Science Advances. 2016 Nov 1;2(11). e1501662. https://doi.org/10.1126/sciadv.1501662