Human papillomavirus type 16 oncoprotein expression is controlled by the cellular splicing factor SRSF2 (SC35).

McFarlane, M. , MacDonald, A. I., Stevenson, A. and Graham, S. V. (2015) Human papillomavirus type 16 oncoprotein expression is controlled by the cellular splicing factor SRSF2 (SC35). Journal of Virology, 89(10), pp. 5276-5287. (doi: 10.1128/JVI.03434-14) (PMID:25717103)

Abstract

High risk human papillomaviruses (HR-HPV) cause anogenital cancers, including cervical cancer, and head and neck cancers. Human papillomavirus type 16 (HPV16) is the most prevalent HR-HPV. HPV oncogenesis is driven by two viral oncoproteins, E6 and E7, which are expressed through alternative splicing of a polycistronic RNA to yield four major splice isoforms (E6 full length, E6*I, E6*II, E6*X). Multiple RNA production from a single gene is controlled by SR splicing factors (SRSFs) and HPV16 infection induces overexpression of a subset of these, SRSFs1, 2 and 3. In this study we examined whether these proteins could control HPV16 oncoprotein expression. siRNA depletion experiments revealed that SRSF1 did not affect oncoprotein RNA levels. While SRSF3 knockdown caused some reduction in E6E7 expression depletion of SRSF2 resulted in a significant loss of E6E7 RNAs resulting in reduced levels of the E6-regulated p53 proteins and E7 oncoprotein itself. SRSF2 contributed to the tumour phenotype of HPV16-positive cervical cancer cells as its depletion resulted in decreased cell proliferation, reduced colony formation and increased apoptosis. SRSF2 did not affect transcription from the P97 promoter that controls viral oncoprotein expression. Rather, RNA decay experiments showed that SRSF2 is required to maintain stability of E6E7 mRNAs. These data show that SRSF2 is a key regulator of HPV16 oncoprotein expression and cervical tumour maintenance.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Graham, Professor Sheila and Stevenson, Mr Andrew and MacDonald, Dr Alasdair and Mcdonald, Dr Melanie
• Authors: McFarlane, M., MacDonald, A. I., Stevenson, A., and Graham, S. V.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Virology
• Publisher: American Society for Microbiology
• ISSN: 0022-538X
• ISSN (Online): 1098-5514