May 11th, 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,
- Ando et al. show that tissue-specific tRNA modifications influence codon decoding and translation efficiency.
- Scazzari et al. demonstrate that stalled disomes are marked by Hel2-dependent ubiquitin chains.
- Dawood et al. use polysome profiling to show that IL-10 and Caspase-8 translation is impaired in PBMCs from hemodialysis patients, despite unchanged transcript levels.
Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation
International Journal of Molecular Sciences, 2025
Ando, D., Rashad, S., Begley, T.J., Endo, H., Aoki, M., Dedon, P.C., & Niizuma, K.
This study investigates how variations in tRNA modifications across different tissues influence codon decoding and protein synthesis. Researchers analysed tRNA expression and modifications in seven mouse tissues, identifying distinct enrichment patterns. Notably, the brain exhibited high levels of queuosine (Q) modifications, while the heart showed elevated mitochondrial tRNA modifications.
tRNA sequencing revealed that there was relatively stable tRNA isoacceptor expression across tissues. However, the study found that differences in tRNA modification stoichiometry significantly affect translation. Ribosome profiling revealed tissue-specific codon usage biases, with the brain and heart favouring G/C-ending codons, contrasting with other tissues’ preference for A/T-ending codons. These biases correlated with the observed tRNA modification patterns.
To assess the functional impact of tRNA modifications, the researchers engineered codon-mutated EGFP constructs, substituting C-ending Q-decoded codons with U-ending counterparts. In vivo experiments demonstrated that these mutations led to reduced EGFP expression in the liver, a tissue with low Q modification levels, but not in the brain, which has high Q levels. This finding underscores the role of tRNA modifications in tissue-specific translation efficiency.
The study concludes that understanding tRNA modification landscapes is crucial for optimizing gene and mRNA therapies, enabling the design of codon usage strategies tailored to specific tissues to enhance therapeutic efficacy.
Stalled disomes marked by Hel2-dependent ubiquitin chains undergo Ubp2/Ubp3-mediated deubiquitination upon translational run-off
Communications Biology, 2025
Scazzari, M., Zhang, Y., Moddemann, A. & Rospert, S.
In this paper, the authors investigate how yeast cells manage stalled ribosomes during protein synthesis. Ribosome stalling can lead to collisions, disrupting protein synthesis and producing incomplete polypeptides. The study focuses on the role of the E3 ubiquitin ligase Hel2, which recognizes these stalled ribosome complexes – specifically disomes and trisomes – and attaches ubiquitin chains to the 40S ribosomal protein Rps20. This ubiquitination serves as a signal for downstream quality control mechanisms.
Using polysome profiling, the researchers found that Hel2 associates more frequently with disomes and trisomes than with monosomes, suggesting that ribosome collisions enhance Hel2 recruitment. They observed that the extent of Rps20 ubiquitination correlates with the duration of ribosome stalling: transient stalls result in mono- or di-ubiquitination, while prolonged stalls lead to tri- or tetra-ubiquitination. This gradation allows the cell to differentiate between short-term and long-term stalling events.
Upon resumption of translation, the deubiquitinases Ubp2 and Ubp3 remove ubiquitin chains from Rps20, facilitating ribosome recycling. The study also highlights the role of Slh1, a component of the ribosome quality control trigger (RQT) complex, in resolving ribosomes with longer ubiquitin chains. In the absence of Slh1, tri- and tetra-ubiquitinated Rps20 species are stabilized, indicating that these more extensively ubiquitinated ribosomes require additional factors for resolution.
In summary, this research elucidates a mechanism by which yeast cells translate the duration of ribosome stalling into specific ubiquitination patterns on Rps20, enabling the ribosome-associated quality control machinery to distinguish between transient and problematic stalls. This system ensures efficient management of stalled ribosomes and maintains cellular protein synthesis integrity.
Learn more about EIRNA Bio’s polysome profiling service here.
Polysome Profiling Proves Impaired IL-10 and Caspase-8 Translation in PBMCs of Hemodialysis Patients
Biomolecules, 2025
Dawood, A., Fiedler, R., Markau, S., Girndt, M., & Ulrich, C.
This study investigates translational control of immune-related genes in peripheral blood mononuclear cells (PBMCs) of hemodialysis (HD) patients, a group known to have impaired immune responses. The researchers applied polysome profiling, a technique that separates mRNAs based on their association with ribosomes, to examine the translation efficiency of specific mRNAs. They focused on interleukin-10 (IL-10), an anti-inflammatory cytokine, and caspase-8, a key mediator of apoptosis.
The study revealed that while the total mRNA levels of IL-10 and caspase-8 were not significantly different between HD patients and healthy controls, their presence in the polysome-associated fractions was markedly reduced in HD patients. This indicates impaired translation of these genes.
The findings point to a selective translational repression of anti-inflammatory and apoptosis-regulating genes in HD patients, which may contribute to their chronic inflammatory state and immune dysfunction. By decoupling mRNA abundance from protein synthesis, the study highlights the importance of translational regulation in disease states and underscores the utility of polysome profiling in translational research.
These insights have potential implications for improving therapeutic strategies aimed at modulating immune function in HD patients, where transcriptional data alone may not fully capture the complexity of gene expression regulation.
Learn more about EIRNA Bio’s polysome profiling services here.