Yeast Dhx29 promotes translation progression by unwinding structured mRNA in the ribosomal A-site
- 1Gene Center Munich, Department of Biochemistry, University of Munich, Germany
Abstract
mRNAs can form stable structures that need to be resolved to facilitate translation. During translation initiation in mammals, the scanning 48S complex requires the helicase activity of DHX29 to unwind stable mRNA structures that cannot be resolved by eIF4A. Here, we show that the yeast DHX29 homolog, Ylr419w (Dhx29), has a similar function during translation on elongating 80S ribosomes. Cryo-EM analyses show that the Dhx29 helicase module is positioned at the mRNA entry channel to engage mRNA, while its double-stranded RNA-binding domain (dsRBD) senses hairpin-forming mRNA in the ribosomal A-site. By selective ribosome profiling, we observed that Dhx29 is associated with transcripts that form RNA structures, such as stable tetraloops. Dhx29 mutants with perturbed helicase activity enrich 80S with hairpins in the A-site, as well as ribosome collisions, while a mutant lacking the N-terminal dsRBD sensor domain loses the specificity for such ribosomes. We thus propose that Dhx29 functions in translation elongation by resolving structured mRNA formed in the ribosomal A-site through its 3'-5' helicase activity and pulling on the mRNA from its 3' end.
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BibTeX
@misc{chitoiu2026yeast,
title = {{Yeast Dhx29 promotes translation progression by unwinding structured mRNA in the ribosomal A-site}},
author = {L. Chitoiu and T. Denk and M. B. D. Müller and O. Berninghausen and T. Becker and M. Thoms and R. Beckmann},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.24.746666},
url = {https://www.biorxiv.org/content/10.64898/2026.08.24.746666v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Yeast Dhx29 promotes translation progression by unwinding structured mRNA in the ribosomal A-site
AU - L. Chitoiu
AU - T. Denk
AU - M. B. D. Müller
AU - O. Berninghausen
AU - T. Becker
AU - M. Thoms
AU - R. Beckmann
PY - 2026
DA - 2026/08/24
PB - bioRxiv
DO - 10.64898/2026.08.24.746666
UR - https://www.biorxiv.org/content/10.64898/2026.08.24.746666v1
AB - mRNAs can form stable structures that need to be resolved to facilitate translation. During translation initiation in mammals, the scanning 48S complex requires the helicase activity of DHX29 to unwind stable mRNA structures that cannot be resolved by eIF4A. Here, we show that the yeast DHX29 homolog, Ylr419w (Dhx29), has a similar function during translation on elongating 80S ribosomes. Cryo-EM analyses show that the Dhx29 helicase module is positioned at the mRNA entry channel to engage mRNA, while its double-stranded RNA-binding domain (dsRBD) senses hairpin-forming mRNA in the ribosomal A-site. By selective ribosome profiling, we observed that Dhx29 is associated with transcripts that form RNA structures, such as stable tetraloops. Dhx29 mutants with perturbed helicase activity enrich 80S with hairpins in the A-site, as well as ribosome collisions, while a mutant lacking the N-terminal dsRBD sensor domain loses the specificity for such ribosomes. We thus propose that Dhx29 functions in translation elongation by resolving structured mRNA formed in the ribosomal A-site through its 3'-5' helicase activity and pulling on the mRNA from its 3' end.
ER -