title: Homologous SV40 RNA trans-splicing: Special case or prime example of viral RNA trans-splicing?
abstract: To date the Simian Virus 40 (SV40) is the only proven example of a virus that recruits the mechanism of RNA trans-splicing to diversify its sequences and gene products. Thereby, two identical viral transcripts are efficiently joined by homologous trans-splicing triggering the formation of a highly transforming 100 kDa super T antigen. Sequences of other viruses including HIV-1 and the human adenovirus type 5 were reported to be involved in heterologous trans-splicing towards cellular or viral sequences but the meaning of these events remains unclear. We computationally and experimentally investigated molecular features associated with viral RNA trans-splicing and identified a common pattern: Viral RNA trans-splicing occurs between strong cryptic or regular viral splice sites and strong regular or cryptic splice sites of the trans-splice partner sequences. The majority of these splice sites are supported by exonic splice enhancers. Splice sites that could compete with the trans-splicing sites for cis-splice reactions are weaker or inexistent. Finally, all but one of the trans-splice reactions seem to be facilitated by one or more complementary binding domains of 11 to 16 nucleotides in length which, however occur with a statistical probability close to one for the given length of the involved sequences. The chimeric RNAs generated via heterologous viral RNA trans-splicing either did not lead to fusion proteins or led to proteins of unknown function. Our data suggest that distinct viral RNAs are highly susceptible to trans-splicing and that heterologous viral trans-splicing, unlike homologous SV40 trans-splicing, represents a chance event.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD4, Level 5, 5 Science Drive 2, Singapore 117597, Singapore.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Poddar
authors.affiliation: INEIDFO GmbH, Weserstrasse 23, 12045 Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Eul
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD4, Level 5, 5 Science Drive 2, Singapore 117597, Singapore.
authors.forename: Volker
authors.initials: V
authors.lastname: Patzel
keywords: Adenovirus; Alternative splicing; HIV-1; RNA trans-splicing; SV40; Viral RNA trans-splicing