Characterization of HPV16 E6E7 intron 1 identifies two novel 5' splice sites and a branch point adenosine at nt 385 for E6*I RNA splicing

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NCI	VIROL-1

Authors

• M Ajiro
• R Jia
• L Zhang
• X Liu
• ZM Zheng

Abstract

HPV16 E6 and E7, two viral oncogenes, are expressed from a single bicistronic pre-mRNA by alternative RNA splicing. In this study, we provide the evidence that the bicistronic pre-mRNA intron 1 contains three 5' splice sites (5' ss) and three 3' splice sites (3' ss). Although all splice sites are used in cervical cancer and its derived cell lines and the choice of two novel alternative 5' ss (nt 221 5' ss and nt 191 5' ss) produces two unknown isoforms of E6E7 mRNAs (E6*V and E6*VI), the nt 226 5' ss and nt 409 3' ss in the pre-mRNA is preferentially selected over the other splice sites crossing over the intron to excise a minimal length of the intron. We identified AACAAAC as the preferred branch point sequence (BPS) and an adenosine at nt 385 (underlined) in the BPS as a branch point to dictate the choice of the nt 409 3' ss for E6*I splicing and E7 viral ocogene expression. Together, our data provide structural basis of the HPV16 E6E7 intron 1 for the expression regulation of viral E6 and E7 oncogenes by alternative RNA splicing.

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