June 1st, 2025
Recent Publications Harnessing the Power of Translatomics
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers,
- Gemin et al. used polysome profiling to investigate the mechanism by which ribosomes bind to the mitochondria during prolonged glucose starvation.
- Zhang et al. used ribosome profiling to evaluate the effect of engineered 5’-UTR regions on recombinant protein expression.
- Duran-Romaña et al. used ribosome profiling to identify locations of protein folding delay and link fold delay to protein aggregation and chaperone dependence.
Ribosomes hibernate on mitochondria during cellular stress
Nature Communications, 2024
Gemin, O., Gluc, M., Rosa, H., Purdy, M., Niemann, M., Peskova, Y., Mattei, S. and Jomaa, A.
In this study, the authors investigate the mechanism by which ribosomes enter a hibernating state and bind to mitochondria during glucose stress in fission yeast. Under prolonged glucose starvation, protein synthesis is halted and ribosomes become attached to the outer mitochondrial membrane via their small subunit. This tethering is mediated by the ribosomal protein Cpc2 (RACK1 ortholog), revealing a novel stress adaptation mechanism.
Using polysome profiling, the authors demonstrated that there is a collapse of active translation by day four of glucose depletion, evidenced by the loss of polysomes and accumulation of 80S monosomes. Cryo-EM was then used in tandem to show that ribosomes isolated during stress were structurally intact but inactive, lacking bound tRNA and mRNA. Notably, it was also observed that the rRNA helix H69 exhibited a conformational change that likely obstructs tRNA or mRNA binding, thus playing a role in halting translation. This mechanism preserves ribosomes in a dormant but recoverable state, positioning them to resume protein synthesis rapidly when conditions improve. The findings have broad implications for understanding cell survival under stress, with relevance to diseases like cancer and neurodegeneration, where metabolic stress and translational control are central.
Learn more about EIRNA Bio’s polysome profiling service here.
Improved recombinant protein expression using the 5′-untranslated region in Chinese hamster ovary cells
International Journal of Biological Macromolecules, 2025
Zhang, H.Y., Fan, Z.L., Wang, C., Li, J.Y., Feng, H.G., Wang, X.Y. and Wang, T.Y.
This study presents a translation-based strategy to increase protein production in CHO cells by modifying 5′-UTR sequences, evaluating the use of uAUGs, uORFs, Kozak motifs, and ribosome-tethering sites to impact expression. By engineering and comparing UTR variations, the authors demonstrate that specific motifs can significantly increase recombinant protein expression. The authors engineered three 5’-UTR sequences, and saw the UTR (UTR-2) containing uORF, ribosome tether sites, and a Kozak sequence improved protein expression by 1.26-1.55 compared to the native UTR.
The authors utilized ribosome profiling to evaluate how the engineered 5′-UTRs affected ribosome distribution and translational efficiency. The study then compared ribosomal occupancy between CHO cells transfected with vectors containing either the native 5′-UTR (UTR-0) or the optimized UTR-2 sequence upstream of HSA. Results showed no significant difference in overall transcript levels, confirming that changes in protein expression were due to translational regulation. The profiling also confirmed minimal structural hindrance within UTR-2, allowing unimpeded scanning by the pre-initiation complex. The findings show that modifications to the URT can effectively modulate ribosome positioning and retention, offering a novel, scalable approach to overcome translational bottlenecks in industrial protein production.
Learn more about EIRNA Bio’s ribosome profiling service here.
Native Fold Delay and its implications for co-translational chaperone binding and protein aggregation
Nature Communications, 2025
Duran-Romaña, R., Houben, B., Migens, P.F., Zhang, Y., Rousseau, F. and Schymkowitz, J.
In this study, the authors introduce the phenomenon of “Native Fold Delay (NFD).” NFD is a metric developed to measure the time between the addition of a residue to a nascent peptide chain, and the addition of the rest of its native interaction partners. The paper examines how this delay exposes aggregation-prone hydrophobic regions, which, if not managed by increased reliance on molecular chaperones, can lead to misfolding or aggregation. The study finds that the yeast Hsp70 chaperone Ssb binds preferentially to these unstructured regions co-translationally, mitigating aggregation risks and promoting correct folding.
Ribosome profiling data revealed that these proteins also exhibit characteristic pausing near domain junctions or slow-folding segments, potentially enabling chaperone access. Further, this suggests that the pauses are evolutionarily selected, rather than a byproduct of translation rate. Profiling also showed increased Ssb binding at these paused ribosomal positions, supporting the hypothesis that folding delay necessitates chaperone protection during synthesis. These findings collectively suggest that ribosome profiling can act as a proxy for identifying folding delays and chaperone dependencies. These insights have broad implications for biotechnology, where optimizing folding efficiency is crucial, and for disease research, especially in neurodegenerative disorders marked by protein aggregation.
Learn more about EIRNA Bio’s ribosome profiling service here.