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Translation is a key determinant controlling the fate of cytoplasmic long non-coding RNAs

Abstract : Summary Despite predicted to lack coding potential, cytoplasmic long non-coding (lnc)RNAs can associate with ribosomes, resulting in some cases into the production of functional peptides. However, the biological and mechanistic relevance of this pervasive 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 translated, which impacts their abundance. We show that XUTs globally accumulate upon translation elongation inhibition, but not when initial ribosome loading is impaired. Translation also affects XUTs independently of NMD, by interfering with their decapping. Ribo-Seq confirmed ribosomes binding to XUTs and identified actively translated small ORFs in their 5’-proximal region. Mechanistic analyses revealed that their NMD-sensitivity depends on the 3’-untranslated region length. Finally, we detected the peptide derived from the translation of an NMD-sensitive XUT reporter in NMD-competent cells. Our work highlights the role of translation in the metabolism of XUTs, which could contribute to expose genetic novelty to the natural selection, while NMD restricts their expression.
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Preprints, Working Papers, ...
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https://hal-cnrs.archives-ouvertes.fr/hal-03853903
Contributor : antonin morillon Connect in order to contact the contributor
Submitted on : Tuesday, November 15, 2022 - 3:11:55 PM
Last modification on : Wednesday, November 16, 2022 - 3:56:51 AM

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Sara Andjus, Ugo Szachnowski, Nicolas Vogt, Isabelle Hatin, Chris Papadopoulos, et al.. Translation is a key determinant controlling the fate of cytoplasmic long non-coding RNAs. 2022. ⟨hal-03853903⟩

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