Despite being predicted to lack coding potential, cytoplasmic long non-coding (lnc)RNAs can associate with ribosomes. However, the landscape and biological relevance of lncRNAs translation remains poorly studied. In yeast, cytoplasmic Xrn1-sensitive lncRNAs (XUTs) are targeted by the Nonsense-Mediated mRNA Decay (NMD), suggesting a translation-dependent degradation process. Here, we report that XUTs are pervasively translated, which impacts their decay. We show that XUTs globally accumulate upon translation elongation inhibition, but not when initial ribosome loading is impaired. Ribo-Seq confirmed ribosomes binding to XUTs and identified actively translated 5’-proximal small ORFs. Mechanistically, the NMD-sensitivity of XUTs mainly depends on the 3’-untranslated region length. Finally, we show that the peptide resulting from the translation of an NMD-sensitive XUT reporter exists in NMD-competent cells. Our work highlights the role of translation in the post-transcriptional metabolism of XUTs. We propose that XUT-derived peptides could be exposed to the natural selection, while NMD restricts XUTs levels.

中文翻译：

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Xrn1 敏感的不稳定长非编码 RNA 在酵母中的普遍翻译

尽管预计细胞质长非编码 (lnc)RNA 缺乏编码潜力，但它可以与核糖体结合。然而，lncRNA 翻译的概况和生物学相关性仍然缺乏研究。在酵母中，细胞质 Xrn1 敏感的 lncRNA (XUT) 是无义介导的 mRNA 衰减 (NMD) 的靶标，表明存在翻译依赖性降解过程。在这里，我们报告 XUT 被普遍翻译，这影响了它们的衰减。我们表明，XUT 在翻译延伸抑制时全局积累，但在初始核糖体负载受损时则不会。Ribo-Seq 证实核糖体与 XUT 结合，并鉴定出主动翻译的 5'-近端小 ORF。从机制上讲，XUT 的 NMD 敏感性主要取决于 3'-非翻译区的长度。最后，我们证明 NMD 敏感的 XUT 报告基因翻译产生的肽存在于 NMD 感受态细胞中。我们的工作强调了翻译在 XUT 转录后代谢中的作用。我们建议 XUT 衍生的肽可以暴露于自然选择，而 NMD 限制 XUT 水平。