Yu Tianxiong, Blyton Michaela B J, Abajorga Milky, Koppetsch Birgit S, Ho Samantha, Xu Bo, Hu Zhongren, Luban Jeremy, Chappell Keith, Weng Zhiping, Theurkauf William E
Department of Genomics and Computational Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia.
Cell. 2025 Apr 17;188(8):2081-2093.e16. doi: 10.1016/j.cell.2025.02.006. Epub 2025 Mar 7.
Koala retrovirus-A (KoRV-A) is spreading through wild koalas in a north-to-south wave while transducing the germ line, modifying the inherited genome as it transitions to an endogenous retrovirus. Previously, we found that KoRV-A is expressed in the germ line, but unspliced genomic transcripts are processed into sense-strand PIWI-interacting RNAs (piRNAs), which may provide an initial "innate" form of post-transcriptional silencing. Here, we show that this initial post-transcriptional response is prevalent south of the Brisbane River, whereas KoRV-A expression is suppressed, promoters are methylated, and sense and antisense piRNAs are equally abundant in a subpopulation of animals north of the river. These animals share a KoRV-A provirus in the MAP4K4 gene's 3' UTR that is spreading through northern koalas and produces hybrid transcripts that are processed into antisense piRNAs, which guide transcriptional silencing. We speculate that this provirus triggers adaptive transcriptional silencing of KoRV-A and is sweeping to fixation.
考拉逆转录病毒A（KoRV - A）正以从北到南的浪潮在野生考拉中传播，同时转导生殖系，在其转变为内源性逆转录病毒的过程中修饰遗传基因组。此前，我们发现KoRV - A在生殖系中表达，但未剪接的基因组转录本被加工成正义链PIWI相互作用RNA（piRNA），这可能提供转录后沉默的初始“先天”形式。在这里，我们表明这种初始的转录后反应在布里斯班河以南很普遍，而在该河北部的一个动物亚群中，KoRV - A的表达受到抑制，启动子被甲基化，正义和反义piRNA同样丰富。这些动物在MAP4K4基因的3'UTR中共享一个KoRV - A前病毒，该前病毒正在通过北部考拉传播，并产生被加工成反义piRNA的杂交转录本，这些反义piRNA指导转录沉默。我们推测这种前病毒触发了KoRV - A的适应性转录沉默，并正在席卷至固定状态。
