Loading…

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

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...

Full description

Saved in:
Bibliographic Details
Published in:Science advances 2016-11, Vol.2 (11), p.e1501662-e1501662
Main Authors: 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
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 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 transcript in breast cancer cells. Consistent with these results, KDM5B expression correlates with shortened in human breast tumor tissues. In contrast, both KDM5A and KDM5B are involved in the lengthening of . Our findings suggest both a novel role for this family of demethylases and a novel targetable mechanism for 3'UTR processing.
ISSN:2375-2548
DOI:10.1126/sciadv.1501662