Repression of beta interferon gene expression in virus-infected cells is correlated with a poly(A) tail elongation.
Expression of beta interferon (IFN-beta) is transiently induced when Namalwa B cells (Burkitt lymphoma cell line) are infected by Sendai virus. In this study, we found that an elongation of the IFN-beta mRNA could be detected in virus-infected cells and that such a modification was not observed when the IFN-beta transcript was induced by a nonviral agent, poly(I-C). Treatment of the cells with a transcriptional inhibitor (actinomycin D or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) resulted in further elongation of the transcript. Characterization of the elongated IFN-beta transcript by primer extension and RNase H treatment showed that the modification was a result of an elongated poly(A) tail of up to 400 nucleotides. We conclude that the poly(A) tail elongation of the IFN-beta transcript is associated with the viral infection. Furthermore, the presence of the elongated IFN-beta transcript correlated with a decrease of IFN-beta protein in the medium and in cell extracts. Sucrose gradient analysis of cytoplasmic extracts showed that IFN-beta transcripts with elongated poly(A) tails were found in the nonpolysomal fractions, whereas the shorter transcripts could be detected in both polysomal and nonpolysomal fractions. A longer form of the IFN-beta mRNA was also found in the nonpolysomal fractions of cells not treated with transcriptional inhibitors. Thus, the observed regulation of IFN-beta mRNA is not entirely dependent on the inhibition of transcription. To our knowledge, this study provides the first example of a poly(A) tail elongation in somatic cells that negatively influences gene expression in vivo.
Dehlin
E
E
Institute of Microbiology and Genetics, Vienna Biocenter, Austria.
von Gabain
A
A
Alm
G
G
Dingelmaier
R
R
Resnekov
O
O
D001483:Base Sequence; D002051:Burkitt Lymphoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D010222:Parainfluenza Virus 1, Human / Q000254:growth & development*; D011061:Poly A / Q000096:biosynthesis*; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011061:Poly A; D016899:Interferon-beta