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Negative regulation of the interferon response by an interferon-induced long non-coding RNA.

Abstract：

:Long non-coding RNAs (lncRNAs) play critical roles in diverse cellular processes; however, their involvement in many critical aspects of the immune response including the interferon (IFN) response remains poorly understood. To address this gap, we compared the global gene expression pattern of primary human hepatocytes before and at three time points after treatment with IFN-α. Among ∼ 200 IFN-induced lncRNAs, one transcript showed ∼ 100-fold induction. This RNA, which we named lncRNA-CMPK2, was a spliced, polyadenylated nuclear transcript that was induced by IFN in diverse cell types from human and mouse. Similar to protein-coding IFN-stimulated genes (ISGs), its induction was dependent on JAK-STAT signaling. Intriguingly, knockdown of lncRNA-CMPK2 resulted in a marked reduction in HCV replication in IFN-stimulated hepatocytes, suggesting that it could affect the antiviral role of IFN. We could show that lncRNA-CMPK2 knockdown resulted in upregulation of several protein-coding antiviral ISGs. The observed upregulation was caused by an increase in both basal and IFN-stimulated transcription, consistent with loss of transcriptional inhibition in knockdown cells. These results indicate that the IFN response involves a lncRNA-mediated negative regulatory mechanism. lncRNA-CMPK2 was strongly upregulated in a subset of HCV-infected human livers, suggesting a role in modulation of the IFN response in vivo.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Kambara H,Niazi F,Kostadinova L,Moonka DK,Siegel CT,Post AB,Carnero E,Barriocanal M,Fortes P,Anthony DD,Valadkhan S

doi

10.1093/nar/gku713

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

10668-80

issue

16

eissn

0305-1048

issn

1362-4962

pii

gku713

journal_volume

42

pub_type

杂志文章

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