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https://doi.org/10.4161/rna.26707
Title: | Homologous SV40 RNA trans-splicing: A new mechanism for diversification of viral sequences and phenotypes | Authors: | Eul, Joachim Volker Patzel |
Keywords: | SV40 100 kD super T antigen alternative splicing cell transformation molecular basis of diseases trans-splicing viral gene expression Alternative Splicing Animals Antigens, Viral, Tumor Base Sequence Binding Sites Cell Line Exons Phenotype RNA Splice Sites RNA, Viral Rats Simian virus 40 Trans-Splicing |
Issue Date: | 1-Nov-2013 | Publisher: | Taylor & Francis | Citation: | Eul, Joachim, Volker Patzel (2013-11-01). Homologous SV40 RNA trans-splicing: A new mechanism for diversification of viral sequences and phenotypes. RNA Biology 10 (11) : 1689-1699. ScholarBank@NUS Repository. https://doi.org/10.4161/rna.26707 | Abstract: | Simian Virus 40 (SV40) is a polyomavirus found in both monkeys and humans, which causes cancer in some animal models. In humans, SV40 has been reported to be associated with cancers but causality has not been proven yet. The transforming activity of SV40 is mainly due to its 94-kD large T antigen, which binds to the retinoblastoma (pRb) and p53 tumor suppressor proteins, and thereby perturbs their functions. Here we describe a 100 kD super T antigen harboring a duplication of the pRB binding domain that was associated with unusual high cell transformation activity and that was generated by a novel mechanism involving homologous RNA trans-splicing of SV40 early transcripts in transformed rodent cells. Enhanced trans-splice activity was observed in clones carrying a single point mutation in the large T antigen 5' donor splice site (ss). This mutation impaired cis-splicing in favor of an alternative trans-splice reaction via a cryptic 5'ss within a second cis-spliced SV40 pre-mRNA molecule and enabled detectable gene expression. Next to the cryptic 5'ss we identified additional trans-splice helper functions, including putative dimerization domains and a splice enhancer sequence. Our findings suggest RNA trans-splicing as a SV40-intrinsic mechanism that supports the diversification of viral RNA and phenotypes. | Source Title: | RNA Biology | URI: | http://scholarbank.nus.edu.sg/handle/10635/138643 | ISSN: | 15476286 15558584 |
DOI: | 10.4161/rna.26707 |
Appears in Collections: | Elements Staff Publications |
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