HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein

Ayslan Castro Brant; Vladimir Majerciak; Miguel Angelo Martins Moreira; Zhi-Ming Zheng

doi:10.1007/s12250-019-00098-0

April 2019

Ayslan Castro Brant, Vladimir Majerciak, Miguel Angelo Martins Moreira and Zhi-Ming Zheng. HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein[J]. Virologica Sinica, 2019, 34(2): 211-221. doi: 10.1007/s12250-019-00098-0

Citation: Ayslan Castro Brant, Vladimir Majerciak, Miguel Angelo Martins Moreira, Zhi-Ming Zheng. HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein .VIROLOGICA SINICA, 2019, 34(2) : 211-221. http://dx.doi.org/10.1007/s12250-019-00098-0

HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein

收稿日期： 2018-12-17
录用日期： 2019-02-21
出版日期： 2019-04-03

HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein

1.
Tumor Virus RNA Biology Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702, USA
2.
Genetics Post-Graduation Program, Rio de Janeiro Federal University, Rio de Janeiro, Brazil
3.
Genetics Program, Nacional Cancer Institute, INCA, Rio de Janeiro 20231-050, Brazil

Corresponding author: Zhi-Ming Zheng, zhengt@exchange.nih.gov
Received Date: 17 December 2018
Accepted Date: 21 February 2019
Published Date: 03 April 2019

Abstract

Human papillomavirus 18 (HPV18) E6 and E7 oncogenes are transcribed as a single bicistronic E6E7 pre-mRNA. The E6 ORF region in the bicistronic E6E7 pre-mRNA contains an intron. Splicing of this intron disrupts the E6 ORF integrity and produces a spliced E6*I RNA for efficient E7 translation. Here we report that the E6 intron has two overlapped branch point sequences (BPS) upstream of its 3' splice site, with an identical heptamer AACUAAC, for E6*I splicing. One heptamer has a branch site adenosine (underlined) at nt 384 and the other at nt 388. E6*I splicing efficiency correlates to the expression level of E6 and E7 proteins and depends on the selection of which branch site. In general, E6*I splicing prefers the 3'ss-proximal branch site at nt 388 over the distal branch site at nt 384. Inactivation of the nt 388 branch site was found to activate a cryptic acceptor site at nt 636 for aberrant RNA splicing. Together, these data suggest that HPV18 modulates its production ratio of E6 and E7 proteins by alternative selection of the two mapped branch sites for the E6*I splicing, which could be beneficial in its productive or oncogenic infection according to the host cell environment.
- Human papillomavirus 18 (HPV18)
- , HPV splicing
- , Branch point
- , E6, E7, E6 intron
- , HPV oncogenes

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