title: Sendai virus trailer RNA binds TIAR, a cellular protein involved in virus-induced apoptosis.
abstract: Sendai virus (SeV) leader (le) and trailer (tr) RNAs are short transcripts generated during abortive antigenome and genome synthesis, respectively. Recom binant SeV (rSeV) that express tr-like RNAs from the leader region are non-cytopathic and, moreover, prevent wild-type SeV from inducing apoptosis in mixed infections. These rSeV thus appear to have gained a function. Here we report that tr RNA binds to a cellular protein with many links to apoptosis (TIAR) via the AU-rich sequence 5' UUUUAAAUUUU. Duplication of this AU-rich sequence alone within the le RNA confers TIAR binding on this le* RNA and a non-cytopathic phenotype to these rSeV in cell culture. Transgenic overexpression of TIAR during SeV infection promotes apoptosis and reverses the anti-apoptotic effects of le* RNA expression. More over, TIAR overexpression and SeV infection act synergistically to induce apoptosis. These short viral RNAs may act by sequestering TIAR, a multivalent RNA recognition motif (RRM) family RNA-binding protein involved in SeV-induced apoptosis. In this view, tr RNA is not simply a by-product of abortive genome synthesis, but is also an antigenome transcript that modulates the cellular antiviral response.
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D010253:Respirovirus Infections / Q000821:virology; D029082:Sendai virus / Q000235:genetics* / Q000472:pathogenicity; D014158:Transcription, Genetic
chemical_list: D012367:RNA, Viral; D016601:RNA-Binding Proteins; C076751:TIAL1 protein, human