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A potential role of inefficient and non-specific piRNA production from the whole transcriptome

Shoji, K.; Tomari, Y.

2026-02-07 genetics
10.1101/2024.01.24.577019 bioRxiv
Show abstract

PIWI-interacting RNAs (piRNAs) safeguard germline genomes from invasive genetic elements such as transposons. While long-term silencing relies on sequence-specific mechanisms such as ping-pong amplification and the incorporation of invader fragments into genomic piRNA clusters, how newly invading elements are initially recognized as "non-self" remains unresolved. Here, we show that low levels of sense-stranded piRNAs are broadly generated from the transcriptome in silkworms, flies, and mice, in direct proportion to RNA abundance and largely independent of canonical piRNA biogenesis pathways. This process can directly sample invaders: in silkworm cells, extremely abundant Bombyx mori latent virus RNAs enter this pathway. Reanalysis of recently endogenized retroviruses reveals distinct stages of adaptation in vivo--mouse AKV remains abundance-coupled, whereas koala KoRV-A has progressed into ping-pong amplification. We propose that this inefficient, non-selective, abundance-coupled pathway constitutes a naive germline surveillance system that seeds an initial piRNA pool for later recruitment into more efficient, specificity-conferring silencing pathways.

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