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


Andjus Sara et al.

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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D-Plex small RNA-seq

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Published
May, 2022

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Products used in this publication

  • Small RNA library preparation with UMI for Illumina
    C05030001
    D-Plex Small RNA-seq Library Prep Kit x24
  • Illumina index primers for D-Plex small RNA library preparation with UMI
    C05030021
    D-Plex Unique Dual Indexes for Illumina - Set A

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