PARP13 regulates cellular mRNA post-transcriptionally and functions as a pro-apoptotic factor by destabilizing TRAILR4 transcript.
PARP13 regulates cellular mRNA post-transcriptionally and functions as a pro-apoptotic factor by destabilizing TRAILR4 transcript.
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DOI：
10.1038/ncomms6362
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发表时间：
2014-11-10
影响因子：
16.6
通讯作者：
Chang P
中科院分区：
文献类型：
--
作者：
Todorova T;Bock FJ;Chang P
聚（ADP-核糖）聚合酶-13（PARP 13/ZAP/ZC 3 HAV 1）是一种抗病毒因子，对特定的RNA病毒如MLV、SINV和HIV有活性。在感染过程中，PARP 13通过其四个CCCH型锌指结构域结合病毒RNA，并通过招募细胞mRNA衰变因子（如外泌体复合物和XRN 1）靶向其降解。在这里，我们表明PARP 13在没有病毒感染的情况下结合并调节细胞mRNA。PARP 13的敲除导致数百种转录本的错误调节。在上调最多的转录物中是编码TRAIL的诱饵受体的TRAILR 4-一种促凋亡细胞因子，其是用于癌症的治疗性抑制的有希望的靶标。PARP 13通过结合其3 'UTR中的区域以外来体依赖性方式使TRAILR 4 mRNA转录后不稳定。因此，PARP 13抑制TRAILR 4表达并增加细胞对TRAIL介导的凋亡的敏感性，作为细胞对TRAIL应答的关键调节剂。
Poly(ADP-ribose) Polymerase-13 (PARP13/ZAP/ZC3HAV1) is an antiviral factor, active against specific RNA viruses such as MLV, SINV and HIV. During infection, PARP13 binds viral RNA via its four CCCH-type zinc finger domains and targets it for degradation by recruiting cellular mRNA decay factors such as the exosome complex and XRN1. Here we show that PARP13 binds to and regulates cellular mRNAs in the absence of viral infection. Knockdown of PARP13 results in the misregulation of hundreds of transcripts. Among the most upregulated transcripts is TRAILR4 that encodes a decoy receptor for TRAIL - a pro-apoptotic cytokine that is a promising target for the therapeutic inhibition of cancers. PARP13 destabilizes TRAILR4 mRNA posttranscriptionally in an exosome dependent manner by binding to a region in its 3’UTR. As a consequence, PARP13 represses TRAILR4 expression and increases cell sensitivity to TRAIL-mediated apoptosis, acting as a key regulator of the cellular response to TRAIL.
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DOI：
10.1016/j.bbagrm.2013.02.003
发表时间：
2013-06
影响因子：
4.7
作者：
Brooks, Seth A.;Blackshear, Perry J.
通讯作者：
Blackshear, Perry J.
影响因子：
5.8
作者：
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通讯作者：
Barredo JC
DOI：
10.1073/pnas.1302564110
发表时间：
2013-07-02
影响因子：
11.1
作者：
Charron, Guillaume;Li, Melody M. H.;Hang, Howard C.
通讯作者：
Hang, Howard C.
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影响因子：
16.8
作者：
Chen, Shoudeng;Xu, Yihui;Liu, Yingfang
通讯作者：
Liu, Yingfang
影响因子：
12.4
作者：
Li, SL;Wilkinson, M;Bhardwaj, A
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Bhardwaj, A