Contributors: Institut Curie Paris; Institut de Biologie Intégrative de la Cellule (I2BC); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS); ANR-15-CE12-0007,DNA-Life,Impact de l'achitecture nucléaire sur la longévité(2015); ANR-19-CE12-0004,ActiMeth,Régulation de l'activité des ribosomes par la 2'-O-méthylation des ARNr : Vers un contrôle de la traduction par l'épitranscriptome de l'ARNr(2019); ANR-10-EQPX-0003,ICGex,Equipement de biologie intégrative du cancer pour une médecine personnalisée(2010); ANR-10-INBS-0009,France Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010); European Project: 616180,EC:FP7:ERC,ERC-2013-CoG,DARK(2014)
Abstract: International audience ; 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.
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