Splicing of a cap-proximal human Papillomavirus 16 E6E7 intron promotes E7 expression, but can be restrained by distance of the intron from its RNA 5' cap.


:Human papillomavirus 16 (HPV16) E6E7 pre-mRNA is bicistronic and has an intron in the E6 coding region with one 5' splice site and two alternative 3' splice sites, which produce E6(*)I and E6(*)II, respectively. If this intron remains unspliced, the resulting E6E7 mRNA expresses oncogenic E6. We found for the first time that the E6E7 pre-mRNA was efficiently spliced in vitro only when capped and that cellular cap-binding factors were involved in the splicing. The cap-dependent splicing of the E6E7 pre-mRNA was extremely efficient in cervical cancer-derived cells, producing mostly E6(*)I, but inefficient in cells transfected with a common retrovirus expression vector, pLXSN16E6E7, due to the large size of this vector's exon 1. Further studies showed that efficient splicing of the E6E7 pre-mRNA depends on the distance of the cap-proximal intron from the RNA 5' cap, with an optimal distance of less than 307nt in order to facilitate better association of U1 small nuclear RNA with the intron 5' splice site. The same was true for splicing of human beta-globin RNA. Splicing of the E6E7 RNA provided more E7 RNA templates and promoted E7 translation, whereas a lack of RNA splicing produced a low level of E7 translation. Together, our data indicate that the distance between the RNA 5' cap and cap-proximal intron is rate limiting for RNA splicing. HPV16 E6E7 pre-mRNA takes advantage of its small cap-proximal exon to confer efficient splicing for better E7 expression.


J Mol Biol


Zheng ZM,Tao M,Yamanegi K,Bodaghi S,Xiao W





Has Abstract


2004-04-09 00:00:00














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    pub_type: 杂志文章


    authors: Barak Z,Lindsley D,Gallant J

    更新日期:1996-03-08 00:00:00

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    authors: Heisig A,Riedel HD,Dobrinski B,Lurz R,Schuster H

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    pub_type: 杂志文章


    authors: Edholm O,Berger O,Jähnig F

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    pub_type: 杂志文章


    authors: Goto Y,Nishikiori S

    更新日期:1991-12-05 00:00:00

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    authors: Yamamoto K,Tokunaga M,Sutoh K,Wakabayashi T,Sekine T

    更新日期:1985-05-25 00:00:00

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    authors: Miller JH,Albertini AM

    更新日期:1983-02-15 00:00:00

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    authors: Dimasi N,Sawicki MW,Reineck LA,Li Y,Natarajan K,Margulies DH,Mariuzza RA

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    authors: Garber MB,Yaremchuk AD,Tukalo MA,Egorova SP,Fomenkova NP,Nikonov SV

    更新日期:1990-08-20 00:00:00

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    authors: Hagervall TG,Pomerantz SC,McCloskey JA

    更新日期:1998-11-20 00:00:00

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    authors: Djuranovic D,Oguey C,Hartmann B

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    authors: Gilbert RJ,Rossjohn J,Parker MW,Tweten RK,Morgan PJ,Mitchell TJ,Errington N,Rowe AJ,Andrew PW,Byron O

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