August 10th, 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,
- Reepmeyer et al. study that substituting Api137’s prolines with 4-fluoro-l-proline altered ribosome binding and activity.
- Roshan et al. investigate that targeting eIF6 sequesters inactive 80S ribosomes by disrupting protein synthesis are essential for cell division and tumour invasiveness.
- De Paolis et al. study that MMR-deficient endometrial cancers share recurrent immunogenic frameshift peptides, supporting development of broad neoantigen vaccines.
Substitution of Proline Residues by 4-Fluoro-l-Proline Affects the Mechanism of the Proline-Rich Antimicrobial Peptide Api137
Antibiotics, 2025
Reepmeyer, M., Krizsan, A., Brakel, A., Kolano, L., Gasse, J., Husselbee, B.W., Robinson, A.J. and Hoffmann, R.
This study examines how substituting proline residues in the proline-rich antimicrobial peptide Api137 with 4-fluoro-l-proline (Fpr) variants affects its antibacterial mechanism. Ribosome profiling was used to reveal how Fpr interacted with translating ribosomes. All six native prolines were individually replaced with either the 4S- or 4R-Fpr stereoisomers, which favour cis- or trans-conformations, respectively. Most substitutions retained antibacterial activity (MICs of 2–4 µg/mL), except for 4S-Fpr at positions 11 and 16, which altered activity notably.
Substitution at Pro11 with 4S-Fpr increased the ribosome-binding inhibitory constant (Kᵢ) by ~28-fold, while 4R-Fpr had no effect—implying a specific binding preference. At the C-terminus, 4R-Fpr at position 16 improved binding (lower Kᵢ) and maintained strong in vitro translation inhibition, whereas 4S-Fpr diminished this function. Overall, these findings highlight that stereochemistry at key prolines critically influences Api137’s binding and inhibitory mechanisms on the bacterial ribosome.
Learn more about EIRNABio’s ribosome profiling service here.
Sequestration of ribosomal subunits as inactive 80S by targeting eIF6 limits mitotic exit and cancer progression
Nucleic Acids Research, 2025
Roshan, P., Biswas, A., Ahmed, S., Anagnos, S., Luebbers, R., Harish, K., Li, M., Nguyen, N., Zhou, G., Tedeschi, F., Hathuc, V., Lin, Z., Hamilton, Z. and Origanti, S.
The authors explore how impairing the function of eukaryotic initiation factor 6 (eIF6) affects ribosome activity, mitotic progression, and cancer behaviour. By using the N106S mutant of eIF6 that disrupts its interaction with the 60S ribosomal subunit, the researchers induced accumulation of inactive 80S ribosomes. Through polysome profiling analysis, this interference in ribosomal subunit dynamics specifically deregulates translation during mitosis, resulting in chromosome segregation defects, delayed mitotic exit, and mitotic catastrophe.
Ribosome profiling (Ribo-Seq) revealed that translation efficiency of key mitotic regulators, particularly mRNAs with long 3′UTRs, was significantly reduced. Polysome profiling analysis showed an accumulation of inactive Functionally, cells bearing the eIF6-N106S mutation exhibited reduced invasive capacity and impaired tumour progression, consistent with eIF6 being overexpressed in aggressive cancers.
Learn more about EIRNABio’s ribosome profiling and polysome profiling services here.
Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer
NPJ Precision Oncology, 2024.
De Paolis, E., Nero, C., Micarelli, E., Leoni, G., Piermattei, A., Trozzi, R., Scarselli, E., D’Alise, A.M., Giacò, L., De Bonis, M., Preziosi, A., Daniele, G., Piana, D., Pasciuto, T., Zannoni, G., Minucci, A., Scambia, G., Urbani, A. and Fanfani, F.
De Paolis et al. investigate the potential for a vaccine targeting shared neoantigens in mismatch repair-deficient (MMRd) endometrial cancer (EC). Using whole-exome sequencing of 35 advanced EC cases, researchers identified a mean of 146 mutated mononucleotide repeats (MNRs), particularly enriched in MLH1-impaired tumours. Many frameshift peptides (FSPs) overlapped with those in the NOUS-209 cancer vaccine, with 80% of patients sharing at least one FSP.
Ribosome profiling (ribo-seq) analysis in an MMRd EC cell line confirmed that most of these mutations were translated into proteins. Immunogenicity testing revealed that several vaccine-matched FSPs elicited T-cell responses in clinical trial participants, supporting their therapeutic potential. The findings suggest MMRd EC harbours recurrent, shared, and immunogenic FSPs, making it a promising target for broad-application neoantigen vaccines, potentially in combination with immune checkpoint inhibitors, and offering preventive possibilities in high-risk groups such as Lynch syndrome.
Learn more about EIRNABio’s ribosome profiling service here.