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Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip

Pradeepa, MM and McKenna, F and Taylor, GCA and Bengani, H and Grimes, GR and Wood, AJ and Bhatia, S and Bickmore, WA (2017) 'Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip.' PLoS Genetics, 13 (4). ISSN 1553-7390

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Abstract

© 2017 Pradeepa et al. Long noncoding RNAs (lncRNAs) have been implicated in various biological functions including the regulation of gene expression, however, the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them. Moreover, little is known about the upstream regulation of lncRNAs. Here we show that the short isoform (p52) of a transcriptional co-activator—PC4 and SF2 interacting protein (Psip1), which is known to be involved in linking transcription to RNA processing, specifically regulates the expression of the lncRNA Hottip–located at the 5’ end of the Hoxa locus. Using both knockdown and knockout approaches we show that Hottip expression is required for activation of the 5’ Hoxa genes (Hoxa13 and Hoxa10/11) and for retaining Mll1 at the 5’ end of Hoxa. Moreover, we demonstrate that artificially inducing Hottip expression is sufficient to activate the 5’ Hoxa genes and that Hottip RNA binds to the 5’ end of Hoxa. By engineering premature transcription termination, we show that it is the Hottip lncRNA molecule itself, not just Hottip transcription that is required to maintains active expression of posterior Hox genes. Our data show a direct role for a lncRNA molecule in regulating the expression of developmentally-regulated mRNA genes in cis.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Pradeepa Madapura Marulasiddappa
Date Deposited: 18 Apr 2017 08:57
Last Modified: 22 Jan 2019 21:15
URI: http://repository.essex.ac.uk/id/eprint/19463

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