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

Julia Reuther; Lukas Schneider; Ioan Iacovache; Andreas Pircher; Walid H Gharib; Benoît Zuber; Norbert Polacek

doi:10.1080/15476286.2021.1935573

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.

Authors

Julia Reuther¹, Lukas Schneider^{1

2}, Ioan Iacovache³, Andreas Pircher^{1

2}, Walid H Gharib⁴, Benoît Zuber³, Norbert Polacek¹

Affiliations

¹ Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.
² Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
³ Institute of Anatomy, University of Bern, Bern, Switzerland.
⁴ Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.

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

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*

Substances

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].