Noncanonical microRNA (miRNA) biogenesis gives rise to retroviral mimics of lymphoproliferative and immunosuppressive host miRNAs.
Noncanonical microRNA (miRNA) biogenesis gives rise to retroviral mimics of lymphoproliferative and immunosuppressive host miRNAs.
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DOI：
10.1128/mbio.00074-14
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发表时间：
2014-04-08
期刊：
影响因子：
6.4
通讯作者：
Sullivan CS
中科院分区：
文献类型：
--
作者：
Kincaid RP;Chen Y;Cox JE;Rethwilm A;Sullivan CS
MicroRNAs(MiRNAs)在真核宿主及其病毒的不同过程中发挥着调节作用，但基本的问题仍然是哪些病毒编码miRNAs及其服务的功能。东半球猴子和猿猴的猿猴泡沫病毒(SFV)可以通过人畜共感染人类，并通过不明确的机制在宿主体内终生感染。在这里，我们报告了SFV通过一种非规范的生物发生模式编码多个miRNAs。SFV的初级miRNA转录本(pri-miRNAs)由RNA聚合酶III(RNAP III)转录，并有多种形式，包括一些被DROSHA切割的形式。然而，这些miRNAs是以上下文相关的方式产生的，因为跨越该区域的较长RNAP II转录本对DROSHA切割具有抵抗力。这表明，该病毒可能会避免任何可能与病毒基因组/转录本切割相关的适应性惩罚。有两个SFV miRNAs与显著的宿主miRNAs具有序列相似性和功能，即淋巴增殖性miRNAmiR-155和天然免疫抑制因子miR-132。这些结果对泡沫病毒生物学、病毒miRNAs和逆转录病毒载体的发展具有重要意义。关于哪些病毒编码miRNAs及其相关功能的基本问题仍然存在。目前，几乎没有报道具有RNA基因组的天然病毒编码miRNAs。猿猴泡沫病毒是一种在非人类宿主种群中流行的逆转录病毒，其中一些可以通过人畜共患病的方式感染猎杀灵长类动物或担任动物看护人的人。我们识别了由SFV编码的一簇miRNAs。对这些miRNAs的表征揭示了进化上保守的、非传统的产生小RNA的机制。一些SFV miRNAs与宿主miRNAs具有相似的序列和功能，包括致癌的miRNAmiR-155和天然免疫抑制因子miR-132。引人注目的是，无关的疱疹病毒也利用这两个相同的调控途径中的一个或两个，这意味着与广泛的病毒相关。这些发现为泡沫病毒生物学和传播学提供了新的见解。
MicroRNAs (miRNAs) play regulatory roles in diverse processes in both eukaryotic hosts and their viruses, yet fundamental questions remain about which viruses code for miRNAs and the functions that they serve. Simian foamy viruses (SFVs) of Old World monkeys and apes can zoonotically infect humans and, by ill-defined mechanisms, take up lifelong infections in their hosts. Here, we report that SFVs encode multiple miRNAs via a noncanonical mode of biogenesis. The primary SFV miRNA transcripts (pri-miRNAs) are transcribed by RNA polymerase III (RNAP III) and take multiple forms, including some that are cleaved by Drosha. However, these miRNAs are generated in a context-dependent fashion, as longer RNAP II transcripts spanning this region are resistant to Drosha cleavage. This suggests that the virus may avoid any fitness penalty that could be associated with viral genome/transcript cleavage. Two SFV miRNAs share sequence similarity and functionality with notable host miRNAs, the lymphoproliferative miRNA miR-155 and the innate immunity suppressor miR-132. These results have important implications regarding foamy virus biology, viral miRNAs, and the development of retroviral-based vectors. Fundamental questions remain about which viruses encode miRNAs and their associated functions. Currently, few natural viruses with RNA genomes have been reported to encode miRNAs. Simian foamy viruses are retroviruses that are prevalent in nonhuman host populations, and some can zoonotically infect humans who hunt primates or work as animal caretakers. We identify a cluster of miRNAs encoded by SFV. Characterization of these miRNAs reveals evolutionarily conserved, unconventional mechanisms to generate small RNAs. Several SFV miRNAs share sequence similarity and functionality with host miRNAs, including the oncogenic miRNA miR-155 and innate immunity suppressor miR-132. Strikingly, unrelated herpesviruses also tap into one or both of these same regulatory pathways, implying relevance to a broad range of viruses. These findings provide new insights with respect to foamy virus biology and vectorology.