A viral Sm-class RNA base-pairs with mRNAs and recruits microRNAs to inhibit apoptosis.
A viral Sm-class RNA base-pairs with mRNAs and recruits microRNAs to inhibit apoptosis.
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DOI：
10.1038/nature24034
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发表时间：
2017-10-12
期刊：
影响因子：
64.8
通讯作者：
Cazalla D
中科院分区：
文献类型：
--
作者：
Gorbea C;Mosbruger T;Cazalla D
病毒表达几类非编码（nc）RNA。对其中大多数人来说，他们的作用和机制是未知的。松鼠猴疱疹病毒（HVS）是一种γ-疱疹病毒，在新世界灵长类动物的T细胞中建立潜伏期，并能够在非天然宿主中引起侵袭性白血病和淋巴瘤，在潜伏感染的细胞中表达7种称为HSUR的小核（sn）、富含U的ncRNA。HSUR与Sm蛋白相关，并与细胞Sm类snRNA共享生物起源和结构特征。其中一种病毒snRNA，HSUR 2，与两种宿主microRNA（miRNAs），miR-142- 3 p和miR-16碱基配对。然而，HSUR 2不影响这两种细胞miRNA的丰度或活性，这表明这些相互作用的替代功能。在这里，我们表明，HSUR 2也与感染细胞中的信使RNA（mRNA）碱基配对。我们结合了体内pepsilen介导的RNA-RNA交联和高通量测序来鉴定HSUR 2靶向的mRNA。HSUR 2靶点包括编码视网膜母细胞瘤（pRb）的mRNA和参与p53信号传导和凋亡的因子。我们发现HSUR 2抑制靶mRNA的表达。HSUR 2与miR-142- 3 p和miR-16之间的碱基配对对于HSUR 2介导的mRNA抑制至关重要，表明HSUR 2招募这两种细胞miRNA靶向mRNA。此外，我们发现HSUR 2利用这种机制来抑制细胞凋亡。我们的研究结果揭示了一个病毒的Sm类RNA作为一个miRNA适配器在后前mRNA加工的基因表达调控的作用。
Viruses express several classes of non-coding (nc) RNAs. For most of them, the functions and mechanisms by which they act are unknown. Herpesvirus saimiri (HVS), a γ-herpesvirus that establishes latency in T cells of New World primates and has the ability to cause aggressive leukemias and lymphomas in non-natural hosts, expresses seven small nuclear (sn), U-rich ncRNAs called HSURs in latently infected cells. HSURs associate with Sm proteins and share biogenesis and structural features with cellular Sm-class snRNAs. One of these viral snRNAs, HSUR 2, base-pairs with two host microRNAs (miRNAs), miR-142-3p and miR-16. However, HSUR 2 does not affect the abundance or activity of these two cellular miRNAs, suggesting alternative functions for these interactions. Here we show that HSUR 2 also base-pairs with messenger RNAs (mRNAs) in infected cells. We combined in vivo psoralen-mediated RNA-RNA crosslinking and high-throughput sequencing to identify mRNAs targeted by HSUR 2. HSUR 2 targets include mRNAs encoding Retinoblastoma (pRb) and factors involved in p53 signaling and apoptosis. We show that HSUR 2 represses expression of target mRNAs. Base-pairing between HSUR 2 and miR-142-3p and miR-16 is essential for HSUR 2-mediated mRNA repression, suggesting that HSUR 2 recruits these two cellular miRNAs to target mRNAs. Furthermore, we show that HSUR 2 utilizes this mechanism to inhibit apoptosis. Our results uncover a role for a viral Sm-class RNA as a miRNA adaptor in post pre-mRNA-processing regulation of gene expression.
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