PDF(Pubmed)
Abstract：
Despite being predicted to lack coding potential, cytoplasmic long noncoding (lnc)RNAs can associate with ribosomes. However, the landscape and biological relevance of lncRNA translation remain poorly studied. In yeast, cytoplasmic Xrn1-sensitive unstable transcripts (XUTs) are targeted by 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 ribosome-associated 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 posttranscriptional metabolism of XUTs. We propose that XUT-derived peptides could be exposed to natural selection, while NMD restricts XUT levels.
摘要：
尽管被预测缺乏编码潜力，细胞质长非编码（lnc）RNA可以与核糖体结合。然而,lncRNAs翻译的景观和生物学相关性仍然缺乏研究。在酵母中，细胞质Xrn1敏感的lncRNAs（XUTs）被无义介导的mRNA衰减（NMD）靶向，这表明了一个依赖于翻译的退化过程。这里,我们报告说，XUT被普遍翻译，影响它们的衰变。我们表明，XUT在翻译延伸抑制时全局积累，但不是当初始核糖体负载受损时。Ribo-Seq证实核糖体与XUT结合，并鉴定出积极翻译的5'近端小ORF。机械上,XUT的NMD敏感性主要取决于3'非翻译区的长度。最后,我们表明，由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。
