Reuther, Julia; Schneider, Lukas; Iacovache, Ioan; Pircher, Andreas; Gharib, Walid H.; Zuber, Benoît; Polacek, Norbert (2021). A small ribosome-associated ncRNA globally inhibits translation by restricting ribosome dynamics. RNA biology, 18(12), pp. 2617-2632. Taylor and Francis 10.1080/15476286.2021.1935573
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A_small_ribosome_associated_ncRNA_globally_inhibits_translation_by_restricting_ribosome_dynamics.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (5MB) | Preview |
Ribosome-associated non-coding RNAs (rancRNAs) have been recognized as an emerging class of regulatory molecules capable of fine-tuning translation in all domains of life. RancRNAs are ideally suited for allowing a swift response to changing environments and are therefore considered pivotal during the first wave of stress adaptation. Previously, we identified an mRNA-derived 18 nucleotides long rancRNA (rancRNA_18) in Saccharomyces cerevisiae that rapidly downregulates protein synthesis during hyperosmotic stress. However, the molecular mechanism of action remained enigmatic. Here, we combine biochemical, genetic, transcriptome-wide and structural evidence, thus revealing rancRNA_18 as global translation inhibitor by targeting the E-site region of the large ribosomal subunit. Ribosomes carrying rancRNA_18 possess decreased affinity for A-site tRNA and impaired structural dynamics. Cumulatively, these discoveries reveal the mode of action of a rancRNA involved in modulating protein biosynthesis at a thus far unequalled precision.
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