TY - JOUR
T1 - A novel antisense RNA ASPACT confers multi-level suppression of PACT and associated signalling
AU - Kuo, Yu Ping
AU - Ma, Chung Pei
AU - Chen, Hui Wen
AU - Chen, Yi Tung
AU - Lai, Yi Hsuan
AU - Liu, Hsuan
AU - Kuo, Rei Lin
AU - Chin-Ming Tan, Bertrand
N1 - Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/9/2
Y1 - 2019/9/2
N2 - 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.
AB - 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.
KW - Antisense non-coding RNA
KW - PACT
KW - epigenetic regulation
KW - interferon
KW - posttranscriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=85067574298&partnerID=8YFLogxK
U2 - 10.1080/15476286.2019.1624471
DO - 10.1080/15476286.2019.1624471
M3 - 文章
C2 - 31135270
AN - SCOPUS:85067574298
SN - 1547-6286
VL - 16
SP - 1263
EP - 1274
JO - RNA Biology
JF - RNA Biology
IS - 9
ER -