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Cell. 2019 Oct 17;179(3):632-643.e12. doi: 10.1016/j.cell.2019.09.002. Epub 2019 Oct 10.

The piRNA Response to Retroviral Invasion of the Koala Genome.

Author information

1
Department of Thoracic Surgery, Clinical Translational Research Center, Shanghai Pulmonary Hospital, The School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3
School of Agriculture and Food Sciences, University of Queensland, Brisbane, Australia.
4
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia. Electronic address: k.chappell@uq.edu.au.
5
Department of Thoracic Surgery, Clinical Translational Research Center, Shanghai Pulmonary Hospital, The School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: zhiping.weng@umassmed.edu.
6
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: william.theurkauf@umassmed.edu.

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.

KEYWORDS:

AKV; KoRV-A; genome invasion; germ-line genome; koala; piRNA; piRNA clusters; retrovirus

PMID:
31607510
PMCID:
PMC6800666
[Available on 2020-10-17]
DOI:
10.1016/j.cell.2019.09.002

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