A small ribosome-associated ncRNA globally inhibits translation by restricting ribosome dynamics

RNA Biol. 2021 Dec;18(12):2617-2632. doi: 10.1080/15476286.2021.1935573. Epub 2021 Jun 13.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism*
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*


  • RNA, Messenger
  • RNA, Untranslated
  • 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].