PiRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Nicholas F. Parrish, Kan Fujino, Yusuke Shiromoto, Yuka Iwasaki, Hongseok Ha, Jinchuan Xing, Akiko Makino, Satomi Kuramochi-Miyagawa, Toru Nakano, Haruhiko Siomi, Tomoyuki Honda, Keizo Tomonaga

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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<sup>-3</sup>-6 × 10<sup>-8</sup>). 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.

Original languageEnglish
Pages (from-to)1691-1703
Number of pages13
JournalRNA
Volume21
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1

Fingerprint

Bornaviridae
Pseudogenes
Nucleoproteins
Mammals
RNA
Small Interfering RNA
Retroelements
Primates
CRISPR-Cas Systems
Antiviral Agents
Rodentia
Genome
Viruses
Callithrix
Messenger RNA
Gene Flow

Keywords

  • CRISPR/Cas
  • Endogenous viral elements
  • Paleovirology
  • PiRNA
  • Retrotransposon

ASJC Scopus subject areas

  • Molecular Biology

Cite this

PiRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals. / Parrish, Nicholas F.; Fujino, Kan; Shiromoto, Yusuke; Iwasaki, Yuka; Ha, Hongseok; Xing, Jinchuan; Makino, Akiko; Kuramochi-Miyagawa, Satomi; Nakano, Toru; Siomi, Haruhiko; Honda, Tomoyuki; Tomonaga, Keizo.

In: RNA, Vol. 21, No. 10, 01.10.2015, p. 1691-1703.

Research output: Contribution to journalArticle

Parrish, NF, Fujino, K, Shiromoto, Y, Iwasaki, Y, Ha, H, Xing, J, Makino, A, Kuramochi-Miyagawa, S, Nakano, T, Siomi, H, Honda, T & Tomonaga, K 2015, 'PiRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals', RNA, vol. 21, no. 10, pp. 1691-1703. https://doi.org/10.1261/rna.052092.115
Parrish, Nicholas F. ; Fujino, Kan ; Shiromoto, Yusuke ; Iwasaki, Yuka ; Ha, Hongseok ; Xing, Jinchuan ; Makino, Akiko ; Kuramochi-Miyagawa, Satomi ; Nakano, Toru ; Siomi, Haruhiko ; Honda, Tomoyuki ; Tomonaga, Keizo. / PiRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals. In: RNA. 2015 ; Vol. 21, No. 10. pp. 1691-1703.
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