ncRNA, Epigenetic and Genome Fluidity, Institut Curie, PSL University, Sorbonne Université, CNRS UMR3244, F-75248 Paris Cedex 05, France.
ncRNA, Epigenetic and Genome Fluidity, Institut Curie, Sorbonne Université, CNRS UMR3244, F-75248 Paris Cedex 05, France.
RNA. 2024 May 16;30(6):662-679. doi: 10.1261/rna.079903.123.
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.
尽管细胞质长非编码 (lnc)RNA 被预测缺乏编码潜力，但它们可以与核糖体结合。然而，lncRNA 翻译的全景和生物学相关性仍未得到充分研究。在酵母中，细胞质 Xrn1 敏感不稳定转录物 (XUT) 是由无意义介导的 mRNA 降解 (NMD) 靶向的，这表明存在翻译依赖性降解过程。在这里，我们报告 XUT 广泛翻译，这会影响它们的降解。我们表明，XUT 在翻译延伸抑制时会全局积累，但初始核糖体加载受损时不会。核糖体测序证实了核糖体与 XUT 的结合，并鉴定了核糖体相关的 5'-近端小 ORF。从机制上讲，XUT 的 NMD 敏感性主要取决于 3'-非翻译区长度。最后，我们表明，来自 NMD 敏感的 XUT 报告者翻译的肽存在于 NMD 有效细胞中。我们的工作强调了翻译在 XUT 转录后代谢中的作用。我们提出，XUT 衍生的肽可能会受到自然选择的影响，而 NMD 会限制 XUT 的水平。
