AI Article Synopsis
- HPV18 E6 and E7 oncogenes are transcribed as a single pre-mRNA, where splicing of an intron in the E6 region produces a variant called E6*I that enhances E7 translation.
- The E6 intron contains two overlapping branch point sequences, both with an identical sequence, influencing splicing efficiency based on which branch site is chosen.
- The preference for the proximal branch site means that HPV18 can adjust the balance of E6 and E7 protein production, potentially aiding its infection process or contributing to cancer development based on the conditions of the host cell.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513837 | PMC |
| http://dx.doi.org/10.1007/s12250-019-00098-0 | DOI Listing |
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