Control of HPV16 E6 intron splicing by a principle of proximity for selection of alternative 5’ and 3’ splice sites and branch points

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NCI	VIROL/MICRO-2

Authors

• M Ajiro
• R Jia
• X Wang
• ZM Zheng

Abstract

HPV16 E6 and E7 are two viral oncoproteins expressed from a single bicistronic pre-mRNA. Splicing of the intron 1 from the E6 ORF is essential for E7 translation, whereas a bicistronic mRNA retaining the intron 1 produces only the E6. Although majority of the intron 1 alternative splicing takes place from nt 226 5' splice site (5' ss) to nt 409 3' splice site (3' ss), we found two minor 3' ss, nt 526 and nt 742 3' ss, are also detectable in HPV16 positive cell lines and cervical cancer tissues. We also identified two additional 5' ss at nt 221 and nt 191. We found that alternative splicing of the HPV16 intron 1 follows a principle of proximity by selection of the nt 226 5’ ss and nt 409 3’ ss over all other alternative splice sites. Further characterization of the E6 intron 1 revealed a tandem array of three alternative branch points guiding the E6 intron splicing. We found that the principle of proximity is also applied for the E6 intron splicing by preferential selection of a nearest branch point in intron 1. Together, this study demonstrated a principle of proximity in splicing of HPV16 intron 1.

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