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bioRxiv · 10.1101/2020.02.05.936112

Conserved small nucleotidic elements at the origin of concerted piRNA biogenesis from genes and lncRNAs

Jensen, S.·Brasset, E.·Parey, E.·Roest Crollius, H.·Sharakhov, I. V.·Vaury, C.
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Abstract

PIWI-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing in animal germ cells. The piRNA pathway is increasingly recognized as critical for essential cellular functions such as germline development and reproduction. In the Anopheles gambiae ovary, as much as 11% of piRNAs map to protein-coding genes. Here we show that ovarian mRNAs and long non-coding RNAs (lncRNAs) are processed into piRNAs that can direct other transcripts into the piRNA biogenesis pathway. Targeting piRNAs fuel transcripts either into the ping-pong cycle of piRNA amplification or into the machinery of phased piRNA biogenesis, thereby creating networks of inter-regulating transcripts. RNAs of the same network share related genomic repeats. These repeats give rise to piRNAs, which target other transcripts and lead to a cascade of concerted RNA slicing. While ping-pong networks are based on repeats of several hundred nucleotides, networks that rely on phased piRNA biogenesis operate through short [~]40-nucleotides long repeats, which we named snetDNAs. Interestingly, snetDNAs are recurring in evolution from insects to mammals. Our study brings to light a new type of a conserved regulatory pathway, the snetDNA-pathway, by which short sequences can include independent genes and lncRNAs in the same biological pathway. AUTHOR SUMMARYSmall RNA molecules are essential actors in silencing mobile genetic elements in animal germ cells. The 24-29-nucleotide-long Piwi-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing. Mosquitoes of the Anopheles gambiae species complex are the principal vectors of malaria, and research on their germline is essential to develop new strategies of vector control by acting on reproduction. In the Anopheles gambiae ovary as much as 11% of piRNAs originate from protein-coding genes. We identified piRNAs which are able to target transcripts from several distinct genes or long non-coding RNAs (lncRNAs), bringing together genic transcripts and lncRNAs in a same regulation network. piRNA targeting induces transcript slicing and production of novel piRNAs, which then target other mRNAs and lncRNAs leading again to piRNA processing, thus resulting in a cascade of RNA slicing and piRNA production. Each network relies on piRNAs originating from repeated genetic elements, present in all transcripts of the same network. Some of these repeats are very short, only [~]40-nucleotides long. We identified similar repeats in all 43 animal species that we analysed, including mosquitoes, flies, arachnidae, snail, mouse, rat and human, suggesting that such regulation networks are recurrent, possibly conserved, in evolutionary history.

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Jensen, S., Brasset, E., Parey, E., Roest Crollius, H., Sharakhov, I. V., Vaury, C.. 2020-02-06. Conserved small nucleotidic elements at the origin of concerted piRNA biogenesis from genes and lncRNAs. https://doi.org/10.1101/2020.02.05.936112

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