PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs essential for fertility. In adult mouse testes, most piRNAs are derived from long single-stranded RNAs lacking annotated open reading frames (ORFs). The mechanisms underlying how piRNA sequences are defined during the cleavages of piRNA precursors remain elusive. Here, we show that 80S ribosomes translate the 5'-proximal short ORFs (uORFs) of piRNA precursors. The MOV10L1/Armitage RNA helicase then facilitates the translocation of ribosomes into the uORF downstream regions (UDRs). The ribosome-bound UDRs are targeted by piRNA processing machinery, with the processed ribosome-protected regions becoming piRNAs. The dual modes of interaction between ribosomes and piRNA precursors underlie the distinct piRNA biogenesis requirements at uORFs and UDRs. Ribosomes also mediate piRNA processing in roosters and green lizards, implying that this mechanism is evolutionarily conserved in amniotes. Our results uncover a function for ribosomes on non-coding regions of RNAs and reveal the mechanisms underlying how piRNAs are defined.

中文翻译：

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核糖体指导长基因间 piRNA 前体上粗线期 piRNA 的形成。

PIWI-interacting RNAs (piRNAs) 是一类对生育能力至关重要的小型非编码 RNA。在成年小鼠睾丸中，大多数 piRNA 来源于缺乏注释的开放阅读框 (ORF) 的长单链 RNA。在 piRNA 前体裂解过程中如何定义 piRNA 序列的机制仍然难以捉摸。在这里，我们展示了 80S 核糖体翻译 piRNA 前体的 5'-近端短 ORF (uORF)。然后，MOV10L1/Armitage RNA 解旋酶促进核糖体易位到 uORF 下游区域 (UDR)。核糖体结合的 UDR 被 piRNA 加工机器靶向，加工后的核糖体保护区域成为 piRNA。核糖体和 piRNA 前体之间相互作用的双重模式是 uORF 和 UDR 的不同 piRNA 生物发生要求的基础。核糖体还介导公鸡和绿蜥蜴的 piRNA 加工，这意味着这种机制在羊膜动物中是进化上保守的。我们的研究结果揭示了核糖体在 RNA 非编码区的功能，并揭示了 piRNA 定义的潜在机制。