Naturally occurring heterologous trans-splicing of adenovirus RNA with host cellular transcripts during infection.
The impact of viral infection on normal host RNA processing remains largely unexplored. We postulated that the high abundance of virally derived nuclear RNA in infected cells could impact host cell RNA splicing and viability. To test for aberrant RNA splicing we examined trans-splicing following infection with the replication-competent adenovirus mutant d11520 that lacks E1B 55 kDa protein. Trans-splicing was observed between viral RNA and several cellular precursor mRNAs, including beta-actin and glyceraldehyde-3-phosphate dehydrogenase. Using a tetracycline-inducible model system simulating viral trans-splicing activity we observed that overexpression of a trans-splicing RNA specifically inhibited cell proliferation. These results demonstrate that heterologous trans-splicing occurs naturally during adenovirus infection and suggest that trans-splicing may contribute to disruption of cell function.
Kikumori
Toyone
T
Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cote
Gilbert J
GJ
Gagel
Robert F
RF
D016475:3T3 Cells; D000199:Actins / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012322:RNA Precursors; D012367:RNA, Viral; D020040:Trans-Splicing; D014157:Transcription Factors / Q000235:genetics*; D014764:Viral Proteins
D000199:Actins; D004268:DNA-Binding Proteins; C051096:MLTF protein, adenovirus; D016271:Proto-Oncogene Proteins c-myc; D012322:RNA Precursors; D012367:RNA, Viral; D014157:Transcription Factors; D014764:Viral Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases