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bioRxiv · 10.1101/2021.10.27.464999

An evolutionarily conserved stop codon enrichment at the 5' ends of mammalian piRNAs

Bornelöv, S.·Czech, B.·Hannon, G. J.
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Abstract

PIWI-interacting RNAs (piRNAs) are small RNAs required to recognize and silence transposable elements. The 5 ends of mature piRNAs are defined through cleavage of long precursor transcripts, primarily by Zucchini (Zuc). Zuc-dependent cleavage typically occurs immediately upstream of a uridine. However, Zuc lacks sequence preference in vitro, pointing towards additional unknown specificity factors. We examined murine piRNAs and revealed a strong and specific enrichment of three sequences (UAA, UAG, UGA)-- corresponding to stop codons--at piRNA 5 ends. Stop codon sequences were also enriched immediately after piRNA processing intermediates, reflecting their Zuc-dependent tail-to-head arrangement. Further analyses revealed that a Zuc in vivo cleavage preference at four sequences (UAA, UAG, UGA, UAC) promotes 5 end stop codons. This observation was conserved across mammals and possibly further. Our work provides new insights into Zuc-dependent cleavage and may point to a previously unrecognized connection between piRNA biogenesis and the translational machinery.

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Bornelöv, S., Czech, B., Hannon, G. J.. 2021-10-27. An evolutionarily conserved stop codon enrichment at the 5' ends of mammalian piRNAs. https://doi.org/10.1101/2021.10.27.464999

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