Abstract
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.
Keywords:
Non-coding rna; l1 stalk; rancRNA; ribosome; translation control.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Protein Biosynthesis*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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RNA, Transfer / genetics
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RNA, Transfer / metabolism*
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RNA, Untranslated / genetics
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RNA, Untranslated / metabolism*
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Ribosomes / genetics
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Ribosomes / metabolism*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism*
Substances
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RNA, Messenger
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RNA, Untranslated
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RNA, Transfer
Grants and funding
This work was supported by the Swiss National Science Foundation [31003A_166527 and 310030_188969 to N.P. and 163761 and 179520 to B.Z.] and in part by the NCCR ‘RNA & Disease’ funded by the Swiss National Science Foundation. J.R. is a recipient of a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft DFG [RE 4041/1–1] and I.I. is a recipient of a grant of the Berne University Research Foundation.Conflict of interest statement. None declaredSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [166527];Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [163761, 179520];Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [188969].