A novel antisense RNA ASPACT confers multi-level suppression of PACT and associated signalling

Yu Ping Kuo, Chung Pei Ma, Hui Wen Chen, Yi Tung Chen, Yi Hsuan Lai, Hsuan Liu, Rei Lin Kuo, Bertrand Chin-Ming Tan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations

Abstract

The innate immune system is the frontline host protection against pathogens. Effective antiviral immunity is elicited upon recognition of viral RNAs by the host pattern recognition receptors. One of the major viral RNA sensors is retinoic acid inducible gene-1, which triggers the production of interferons (IFNs). In turn, this protective response requires another viral sensor and immunity factor interferon-inducible protein kinase RNA activator (PACT/PRKRA). Here, we report the identification and characterization of a novel antisense PACT gene that expresses a non-coding RNA in a convergent and interferon-inducible manner. Publicly available gene structure and expression data revealed that this gene, that we termed ASPACT, overlaps with the 3′ -end of the PACT locus and is highly expressed during viral infection. Our results confirm the IFN-β-inducibility of ASPACT, which is dependent on STAT-1/2. We further discovered that downregulation of ASPACT impacts both the expression and localization of the PACT transcript. At the transcription level, ChIP and ChIRP assays demonstrated that the ASPACT non-coding RNA occupies distinct chromatin regions of PACT gene and is important for promoter recruitment of the epigenetic silencer HDAC1. In parallel, ASPACT was also found to mediate nuclear retention of the PACT mRNA via direct RNA–RNA interaction, as revealed by RNA antisense purification assay. In summary, our results support the model that the non-coding RNA ASPACT acts as a negative regulator of PACT at multiple levels, and reveal a novel regulator of the viral counteractive response.

Original languageEnglish
Pages (from-to)1263-1274
Number of pages12
JournalRNA Biology
Volume16
Issue number9
DOIs
StatePublished - 02 09 2019

Bibliographical note

Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Antisense non-coding RNA
  • PACT
  • epigenetic regulation
  • interferon
  • posttranscriptional regulation

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