Abstract
Piwi-interacting (pi-) RNAs guide germline-expressed Piwi proteins in order to suppress the activity of transposable elements (TEs). But notably, the majority of pachytene piRNAs in mammalian testes is not related to TEs. This raises the question of whether the Piwi/piRNA pathway exerts functions beyond TE silencing. Although gene-derived piRNAs were described many times, a possible gene-regulatory function was doubted due to the absence of antisense piRNAs. Here we sequenced and analyzed piRNAs expressed in the adult testis of the pig, as this taxon possesses the full set of mammalian Piwi paralogs while their spermatozoa are marked by an extreme fitness due to selective breeding. We provide an exhaustive characterization of porcine piRNAs and genomic piRNA clusters. Moreover, we reveal that both sense and antisense piRNAs derive from protein-coding genes, while exhibiting features that clearly show that they originate from the Piwi/piRNA-mediated post-transcriptional silencing pathway, commonly referred to as ping-pong cycle. We further show that the majority of identified piRNA clusters in the porcine genome spans exonic sequences of protein-coding genes or pseudogenes, which reveals a mechanism by which primary antisense piRNAs directed against mRNA can be generated. Our data provide evidence that spliced mRNAs, derived from such loci, are not only targeted by piRNAs but are also subject to ping-pong cycle processing. Finally, we demonstrate that homologous genes are targeted and processed by piRNAs in pig, mouse and human. Altogether, this strongly suggests a conserved role for the mammalian Piwi/piRNA pathway in post-transcriptional regulation of protein-coding genes, which did not receive much attention so far.
Highlights
Small non-coding RNAs are involved in many cellular processes such as gene regulation, transposon repression and antiviral defense, which they realize by the principle of RNA interference [1]
Our present study strongly indicates that the mammalian Piwi/piRNA system is involved in post-transcriptional gene regulation and that piRNA clusters, which occupy a central role in this process, might be more dynamic and adaptable than previously thought
We found that the insertion direction correlates well with, and can explain the different sense/antisense piRNA ratios for the most prominent transposable elements (TEs) classes, namely tRNA-derived short interspersed elements (SINEs), L1 and ERV1 (S1 Fig), which comprise more than three quarters of all TE-derived piRNA reads
Summary
Small non-coding RNAs (sncRNAs or sRNAs) are involved in many cellular processes such as gene regulation, transposon repression and antiviral defense, which they realize by the principle of RNA interference [1]. To fulfill their functions all types of sRNA are dependent on Argonaute proteins, for which they act as guides that recognize targets based on sequence complementarity. Piwi Mediated Gene Regulation Is Conserved in Mammals The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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