最近,大量证据表明,假基因衍生的长链非编码RNA(lncRNA)作为调节RNA通过与DNA的多种功能相互作用模式参与基本生理过程和疾病发展,RNA,和蛋白质。这里,我们报道了鸟苷酸结合蛋白1的假基因GBP1P1在调节甲型流感病毒(IAV)在A549细胞中的复制中的重要作用。GBP1P1在IAV感染后显著上调,由JAK/STAT信令控制。功能上,GBP1P1在A549细胞中的异位表达导致IAV复制的显著抑制。相反,沉默GBP1P1促进IAV复制和病毒产生,表明GBP1P1是干扰素诱导的抗病毒效应物之一。机械上,GBP1P1位于细胞质中,并充当捕获DHX9(DExH盒解旋酶9)的海绵,随后限制IAV复制。一起,这些研究表明GBP1P1在拮抗IAV复制中起重要作用。IMPORTANCELong非编码RNA(lncRNA)在哺乳动物细胞中广泛表达,并在各种生物过程中作为调节剂发挥关键作用。越来越多的证据表明,宿主编码的lncRNAs是参与宿主-病毒相互作用的重要调节因子。这里,我们定义了GBP1P1作为诱饵与病毒mRNAs竞争DHX9结合的新功能。我们证明IAV诱导GBP1P1是由JAK/STAT激活介导的。此外,GBP1P1具有抑制IAV复制的能力。重要的是,我们揭示了GBP1P1作为诱饵结合和滴定DHX9远离病毒mRNA,从而减弱病毒生产。这项研究为以前未表征的GBP1P1(一种假基因衍生的lncRNA)的作用提供了新的见解,在宿主抗病毒过程中进一步了解复杂的GBP网络。
Recently, substantial evidence has demonstrated that pseudogene-derived long noncoding RNAs (lncRNAs) as regulatory RNAs have been implicated in basic physiological processes and disease development through multiple modes of functional interaction with DNA, RNA, and proteins. Here, we report an important role for GBP1P1, the pseudogene of guanylate-binding protein 1, in regulating influenza A virus (IAV) replication in A549 cells. GBP1P1 was dramatically upregulated after IAV infection, which is controlled by JAK/STAT signaling. Functionally, ectopic expression of GBP1P1 in A549 cells resulted in significant suppression of IAV replication. Conversely, silencing GBP1P1 facilitated IAV replication and virus production, suggesting that GBP1P1 is one of the interferon-inducible antiviral effectors. Mechanistically, GBP1P1 is localized in the cytoplasm and functions as a sponge to trap
DHX9 (DExH-box helicase 9), which subsequently restricts IAV replication. Together, these studies demonstrate that GBP1P1 plays an important role in antagonizing IAV replication.IMPORTANCELong noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as regulators in various biological processes. A growing body of evidence suggests that host-encoded lncRNAs are important regulators involved in host-virus interactions. Here, we define a novel function of GBP1P1 as a decoy to compete with viral mRNAs for
DHX9 binding. We demonstrate that GBP1P1 induction by IAV is mediated by JAK/STAT activation. In addition, GBP1P1 has the ability to inhibit IAV replication. Importantly, we reveal that GBP1P1 acts as a decoy to bind and titrate
DHX9 away from viral mRNAs, thereby attenuating virus production. This study provides new insight into the role of a previously uncharacterized GBP1P1, a pseudogene-derived lncRNA, in the host antiviral process and a further understanding of the complex GBP network.