Identifying regulatory elements and their RNA-binding proteins in the 3' untranslated regions of papillomavirus late mRNAs

Iamborwornkun,Nuttawan; Kitkumthorn,Nakarin; Stevenson,Andrew; Kirk,Anna; Graham,Sheila V.; Chuen-im,Thanaporn

doi:10.3892/br.2024.1813

Identifying regulatory elements and their RNA-binding proteins in the 3' untranslated regions of papillomavirus late mRNAs

Authors:
- Nuttawan Iamborwornkun
- Nakarin Kitkumthorn
- Andrew Stevenson
- Anna Kirk
- Sheila V. Graham
- Thanaporn Chuen-im
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Affiliations: Department of Microbiology, Faculty of Science, Silpakorn University, Sanam Chandra Palace Campus, Nakhon Pathom 73000, Thailand, Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand, MRC-University of Glasgow Centre for Virus Research, School of Infection and Immunity, College of Medical Veterinary and Life Sciences University of Glasgow, Glasgow, G61 1QH, UK
Published online on: July 1, 2024 https://doi.org/10.3892/br.2024.1813
Article Number: 125
Copyright: © Iamborwornkun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human papillomaviruses (HPVs) infect cutaneous and mucosal epithelia to cause benign (warts) and malignant lesions (e.g. cervical cancer). Bovine papillomaviruses (BPVs) infect fibroblasts to cause fibropapillomas but can also infect cutaneous epithelial cells. For HPV-1, -16, -31 and BPV-1, cis-acting RNA elements in the late 3' untranslated region (3'UTR) control expression of virus proteins by binding host cell proteins. The present study compared the effects on gene expression of the cis-acting elements of seven PV late 3'UTRs (HPV-6b, -11, -16, -31 and BPV-1, -3 and -4) representing a range of different genera and species and pathological properties. pSV-beta-galactosidase reporter plasmids containing the late 3'UTRs from seven PVs were transiently transfected into cervical adenocarcinoma HeLa cells, and reporter gene expression quantified by reverse transcription-quantitative PCR and a beta-galactosidase assay. All elements inhibited gene expression in keratinocytes. Cancer-related types HPV-16 and -31, had the greatest inhibitory activity whereas the lowest inhibition was found in the non-cancer related types, BPV-3 and HPV-11. Using RBPmap version 1.1, bioinformatics predictions of factors binding the elements identified proteins which function mainly in mRNA splicing. Markedly, in terms of protein binding motifs, BPV late 3'UTR elements were similar to those of HPV-1a but not to other HPVs. Using HPV-1a as a model and siRNA depletion, the bioinformatics predictions were tested and it was found that PABPC4 was responsible for some of the 3'UTR repressive activity. The data revealed candidate proteins that could control PV late gene expression.

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