Negative regulation of the interferon response by an interferon-induced long non-coding RNA.
Negative regulation of the interferon response by an interferon-induced long non-coding RNA.
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DOI：
10.1093/nar/gku713
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发表时间：
2014
影响因子：
14.9
通讯作者：
Valadkhan S
中科院分区：
文献类型：
--
作者：
Kambara H;Niazi F;Kostadinova L;Moonka DK;Siegel CT;Post AB;Carnero E;Barriocanal M;Fortes P;Anthony DD;Valadkhan S
长非编码RNA(LncRNAs)在多种细胞过程中发挥重要作用；然而，它们参与免疫反应的许多关键方面，包括干扰素(IFN)反应，目前仍知之甚少。为了解决这一差距，我们比较了干扰素-α治疗前和治疗后三个时间点的原代人肝细胞的整体基因表达模式。在∼200干扰素诱导的lncRNA中，有一个转录本显示∼的诱导倍数为100倍。这种RNA被我们命名为lncRNA-CMPK2，它是由干扰素在人和小鼠不同类型的细胞中诱导的一种剪接的、多腺化的核转录本。与蛋白质编码的干扰素刺激基因(ISGs)相似，它的诱导依赖于JAK-STAT信号。有趣的是，敲除lncRNA-CMPK2导致干扰素刺激的肝细胞中丙型肝炎病毒复制显著减少，这表明它可能影响干扰素的抗病毒作用。我们可以证明，lncRNA-CMPK2基因敲除导致了几个蛋白质编码的抗病毒ISG的上调。观察到的上调是由基础转录和干扰素刺激的转录增加引起的，这与基因敲除细胞的转录抑制消失一致。这些结果表明，干扰素应答涉及一种由lncRNA介导的负性调节机制。LncRNA-CMPK2在丙型肝炎病毒感染的人肝脏中强烈上调，表明在体内对干扰素反应的调节作用。
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.
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影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
64.5
作者：
Gomez JA;Wapinski OL;Yang YW;Bureau JF;Gopinath S;Monack DM;Chang HY;Brahic M;Kirkegaard K
通讯作者：
Kirkegaard K
影响因子：
4.5
作者：
Kutter C;Watt S;Stefflova K;Wilson MD;Goncalves A;Ponting CP;Odom DT;Marques AC
通讯作者：
Marques AC
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
DOI：
10.1084/jem.20112343
发表时间：
2012-04-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fang TC;Schaefer U;Mecklenbrauker I;Stienen A;Dewell S;Chen MS;Rioja I;Parravicini V;Prinjha RK;Chandwani R;MacDonald MR;Lee K;Rice CM;Tarakhovsky A
通讯作者：
Tarakhovsky A