Multi-protein Bridging Factor 1(Mbf1), Rps3 and Asc1 prevent stalled ribosomes from frameshifting

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Abstract

Reading frame maintenance is critical for accurate translation. We show that the conserved eukaryotic/archaeal protein Mbf1 acts with ribosomal proteins Rps3/uS3 and eukaryotic Asc1/RACK1 to prevent frameshifting at inhibitory CGA-CGA codon pairs in the yeast Saccharomyces cerevisiae. Mutations in RPS3 that allow frameshifting implicate eukaryotic conserved residues near the mRNA entry site. Mbf1 and Rps3 cooperate to maintain the reading frame of stalled ribosomes, while Asc1 also mediates distinct events that result in recruitment of the ribosome quality control complex and mRNA decay. Frameshifting occurs through a +1 shift with a CGA codon in the P site and involves competition between codons entering the A site, implying that the wobble interaction of the P site codon destabilizes translation elongation. Thus, eukaryotes have evolved unique mechanisms involving both a universally conserved ribosome component and two eukaryotic-specific proteins to maintain the reading frame at ribosome stalls.

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All data generated or analyzed during this study are included in the manuscript and supporting files.

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Jiyu Wang

Department of Biochemistry and Biophysics, University of Rochester, Rochester, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1283-2934
Jie Zhou

Department of Biochemistry and Biophysics, University of Rochester, Rochester, United States

Competing interests
The authors declare that no competing interests exist.
Qidi Yang

Department of Biochemistry and Biophysics, University of Rochester, Rochester, United States

Competing interests
The authors declare that no competing interests exist.
Elizabeth J Grayhack

Department of Biochemistry and Biophysics, University of Rochester, Rochester, United States

For correspondence
elizabeth_grayhack@urmc.rochester.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2400-5490

Funding

NIH Office of the Director (R01 GM118386)

Elizabeth J Grayhack

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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