Alternative splicing dictates translational start in Epstein-Barr virus transcripts.
Of the 10 viral genes known to be expressed during Epstein-Barr virus (EBV) latency, six encode nuclear antigens (EBNAs), all of which are expressed from a long primary transcript by means of alternative splicing and alternative polyadenylation sites. The primary transcript is generated by either of two promoters which operate in a mutually exclusive fashion in different clonal cell lines. All mRNAs from either promoter have exons in common from the BamHI W viral genomic fragment (the major internal repeat, IR1) which encode the N-terminal portion of one of the nuclear antigens (EBNA 4). In addition to the coding regions for EBNA 4, EBNA mRNAs encode another EBNA (i.e. EBNA 1, 2, 3A, 3B or 3C) downstream. We show that alternative splicing determines whether the translation initiation codon for EBNA 4 is present or absent, thus permitting the generation of mRNAs in which the first translation initiation codon is either that for the EBNA 4 gene or for the other EBNA gene encoded downstream. This mechanism presumably ensures efficient translation of all the EBNA genes.
Rogers
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RP
Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, MA.
Woisetschlaeger
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Speck
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SH
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D003062:Codon / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens; D015723:Gene Library; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D000956:Antigens, Viral; D003062:Codon; D019309:Epstein-Barr Virus Nuclear Antigens; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012367:RNA, Viral