piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals.
piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals.
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DOI：
10.1261/rna.052092.115
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Tomonaga K
中科院分区：
文献类型：
--
作者：
Parrish NF;Fujino K;Shiromoto Y;Iwasaki YW;Ha H;Xing J;Makino A;Kuramochi-Miyagawa S;Nakano T;Siomi H;Honda T;Tomonaga K
内源性博尔纳病毒样核蛋白元件（Endogenous bornavirus-like nucleoprotein elements，EBLN）是脊椎动物基因组中由古老的博尔纳病毒核蛋白mRNA通过宿主反转录转座子机制逆转录和整合而获得的序列。虽然具有EBLN的物种似乎对博纳病毒病具有相对抗性，但这种关联的性质尚不清楚。我们假设EBLN可以产生PIWI相互作用RNA（piRNA）形式的抗病毒干扰RNA，这是一类已知可以沉默转座子但不沉默外源病毒的小RNA。我们发现，在大约2500万~ 4000万年前独立获得EBLN的啮齿类动物和灵长类动物中，EBLN出现在基因组的piRNA生成区域中的频率远远高于预期的偶然性（λ = 8 × 10−3-6 × 10−8）。七个人EBLN中的三个落在注释的皮尔纳簇内，两个绒猴EBLN产生真正的piRNA。在大鼠和小鼠中，五种EBLN中的至少两种在雄性性腺中产生丰富的piRNA。虽然在啮齿动物和灵长类动物之间没有EBLN是同线性的，但一些含有EBLN的皮尔纳簇是同线性的;因此我们推断EBLN整合到现有的皮尔纳簇中。所有来源于EBLN的真正piRNA相对于提出的古博纳病毒核蛋白mRNA是反义的。这些观察结果与EBLN衍生的piRNA样RNA在干扰古博纳病毒感染中的作用一致。他们提出了一个假设，即逆转录转座子依赖的病毒-宿主基因流可以在后生动物中产生RNA介导的序列特异性抗病毒免疫记忆，类似于原核生物中的CRISPR/Cas系统。
Endogenous bornavirus-like nucleoprotein elements (EBLNs) are sequences within vertebrate genomes derived from reverse transcription and integration of ancient bornaviral nucleoprotein mRNA via the host retrotransposon machinery. While species with EBLNs appear relatively resistant to bornaviral disease, the nature of this association is unclear. We hypothesized that EBLNs could give rise to antiviral interfering RNA in the form of PIWI-interacting RNAs (piRNAs), a class of small RNA known to silence transposons but not exogenous viruses. We found that in both rodents and primates, which acquired their EBLNs independently some 25–40 million years ago, EBLNs are present within piRNA-generating regions of the genome far more often than expected by chance alone (ℙ = 8 × 10−3–6 × 10−8). Three of the seven human EBLNs fall within annotated piRNA clusters and two marmoset EBLNs give rise to bona fide piRNAs. In both rats and mice, at least two of the five EBLNs give rise to abundant piRNAs in the male gonad. While no EBLNs are syntenic between rodent and primate, some of the piRNA clusters containing EBLNs are; thus we deduce that EBLNs were integrated into existing piRNA clusters. All true piRNAs derived from EBLNs are antisense relative to the proposed ancient bornaviral nucleoprotein mRNA. These observations are consistent with a role for EBLN-derived piRNA-like RNAs in interfering with ancient bornaviral infection. They raise the hypothesis that retrotransposon-dependent virus-to-host gene flow could engender RNA-mediated, sequence-specific antiviral immune memory in metazoans analogous to the CRISPR/Cas system in prokaryotes.
影响因子：
3.7
作者：
Sagy O;Shamir R;Rechavi O
通讯作者：
Rechavi O