澳大利亚昆士兰大学Keith Chappell、美国麻省大学医学院Zhiping Weng、William E. Theurkauf研究组，合作发现piRNA对考拉基因组逆转录病毒入侵的反应。2019年10月10日，《细胞》在线发表了这一最新研究成果。
KoRV-Aγ逆转录病毒感染体细胞和生殖细胞，并通过水平和垂直转移相结合的方式席卷野生考拉，利用KoRV-Aγ逆转录病毒的这种特性可以直接分析逆转录病毒入侵生殖细胞系基因组的情况。 γ逆转录病毒会产生剪接的Env mRNA和编码Gag、Pol和病毒基因组的未剪接的转录本，但KoRV-A piRNA几乎完全来自未剪接的基因组转录本，并且具有强烈的有义链偏向性。
值得注意的是，从昆虫到胎盘哺乳动物，未剪接的原病毒piRNA转录本的处理都是保守的。研究人员推测绕过的剪接产生了一个保守的分子模式，该模式将前病毒基因组转录本引导到piRNA的发生机制，并且这种“先天”的piRNA反应在产生反义piRNA前抑制了转座，从而建立了序列特异性的适应性免疫。
据了解，反义Piwi相互作用RNA（piRNA）调控生殖发育过程中已建立的转座子的沉默，有义piRNA驱动反义池的“乒乓”扩增，但生殖细胞系如何响应基因组入侵尚不清楚。
附：英文原文
Title: The piRNA Response to Retroviral Invasion of the Koala Genome
Author: Tianxiong Yu, Birgit S. Koppetsch, Sara Pagliarani, Stephen Johnston, Noah J. Silverstein, Jeremy Luban, Keith Chappell, Zhiping Weng, William E. Theurkauf
Issue&Volume: 10 October 2019
Abstract:
Antisense Piwi-interacting RNAs (piRNAs) guide silencing of established transposons during germline development, and sense piRNAs drive ping-pong amplification of the antisense pool, but how the germline responds to genome invasion is not understood. The KoRV-A gammaretrovirus infects the soma and germline and is sweeping through wild koalas by a combination of horizontal and vertical transfer, allowing direct analysis of retroviral invasion of the germline genome. Gammaretroviruses produce spliced Env mRNAs and unspliced transcripts encoding Gag, Pol, and the viral genome, but KoRV-A piRNAs are almost exclusively derived from unspliced genomic transcripts and are strongly sense-strand biased. Significantly, selective piRNA processing of unspliced proviral transcripts is conserved from insects to placental mammals. We speculate that bypassed splicing generates a conserved molecular pattern that directs proviral genomic transcripts to the piRNA biogenesis machinery and that this “innate” piRNA response suppresses transposition until antisense piRNAs are produced, establishing sequence-specific adaptive immunity.
DOI: 10.1016/j.cell.2019.09.002
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31008-6