Differential expression of PPP1R12A transcripts, including those harbouring alternatively spliced micro-exons, in placentae from complicated pregnancies

Frew, Edward, Sainty, Rebecca, Chappell-Maor, Louise, Bone, Caitlin, Daskeviciute, Dagne, Russell, Sarah, Buhigas, Claudia, Iglesias-Platas, Isabel, Lartey, Jon and Monk, David (2024) Differential expression of PPP1R12A transcripts, including those harbouring alternatively spliced micro-exons, in placentae from complicated pregnancies. Placenta, 151. pp. 1-9. ISSN 0143-4004

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Abstract

Introduction Placenta-associated pregnancy complications, including pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are conditions postulated to originate from initial failure of placentation, leading to clinical sequelae indicative of endothelial dysfunction. Vascular smooth muscle aberrations have also been implicated in the pathogenesis of both disorders via smooth muscle contractility and relaxation mediated by Myosin Light Chain Phosphatase (MLCP) and the oppositional contractile action of Myosin Light Chain Kinase. PPP1R12A is a constituent part of the MLCP complex responsible for dephosphorylation of myosin fibrils. We hypothesize that alternative splicing of micro-exons result in isoforms lacking the functional leucine zipper (LZ) domain which may give those cells expressing these alternative transcripts a tendency towards contraction and vasoconstriction. Methods Expression was determined by qRT-PCR. Epigenetic profiling consisted of bisulphite-based DNA methylation analysis and ChIP for underlying histone modifications. Results We identified several novel transcripts with alternative micro-exon inclusion that would produce LZ- PPP1R12A protein. qRT-PCR revealed some isoforms, including the PPP1R12A canonical transcript, are differentially expressed in placenta biopsies from PE and IUGR samples compared to uncomplicated pregnancies. Discussion We propose that upregulation of PPP1R12A expression in complicated pregnancies may be due to enhanced promoter activity leading to increased transcription as a response to physiological stress in the placenta, which we show is independent of promoter DNA methylation.

Item Type:	Article
Uncontrolled Keywords:	dna methylation,micro-exons,ppp1r12a,placenta,reproductive medicine,obstetrics and gynaecology,developmental biology ,/dk/atira/pure/subjectarea/asjc/2700/2743
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Wheeler Group
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	19 Apr 2024 14:30
Last Modified:	30 Apr 2024 08:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/94981
DOI:	10.1016/j.placenta.2024.04.005

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