July 27th, 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,
- Susanto et al. introduce RAPIDASH, a tag-free method to profile ribosome-associated proteins, uncovering dynamic changes in translation machinery across embryonic tissues, cancer cells, and macrophages.
- De Paolis et al. characterize shared frameshift-derived neoantigens in mismatch repair–deficient endometrial cancer, revealing strong candidates for off-the-shelf cancer vaccines.
- Zang et al. describe a circular RNA–encoded peptide that blocks immunogenic ferroptosis by disrupting STAT1 signalling, offering new strategies to enhance immune checkpoint therapy.
Together, these studies advance our understanding of translational control, tumour immunity, and personalized immunotherapy.
RAPIDASH: Tag-free enrichment of ribosome-associated proteins reveals composition dynamics in embryonic tissue, cancer cells, and macrophages
Molecular Cell, 2024
Teodorus Theo Susanto, Victoria Hung, Andrew G. Levine, Yuxiang Chen, Craig H. Kerr, Yongjin Yoo, Juan A. Oses-Prieto, Lisa Fromm, Zijian Zhang, Travis C. Lantz, Kotaro Fujii, Marius Wernig, Alma L. Burlingame, Davide Ruggero, and Maria Barna
This paper presents a novel, label-free method to isolate ribosomes along with ribosome associated proteins (RAPs) across diverse biological samples. Traditional methods struggled to capture RAPs broadly due to dependency on tags or specific cell types. RAP identification by affinity to sulfhydryl-charged resin (RAPIDASH) overcomes this by using resin-based purification and ultracentrifugation to enrich ribosome–RAP complexes from any sample without genetic modification.
Applying RAPIDASH to mouse embryonic tissues, researchers identified hundreds of RAP candidates, including DHX30 and LLPH, two proteins enriched in the developing forebrain with roles in neurodevelopment. Functionally, LLPH was shown to regulate the translation of mRNAs encoding long proteins, highlighting its biological importance in the brain. In cancer cell lines, RAPIDASH detected cancer-specific changes in ribosome composition, while in macrophages activated by LPS or poly(I:C) it revealed extensive, stimulus-dependent remodelling of RAP profiles post-stimulation.
By enabling tag-free, proteomic-scale RAP enrichment across organisms and conditions, RAPIDASH allows unbiased discovery of ribosomal heterogeneity and its dynamics. This opens new avenues for understanding how ribosome-associated proteins regulate translation in development, disease, and immune responses. The methodology provides a broadly applicable platform to reveal context-specific ribosomal regulation and potential therapeutic targets.
Learn more about EIRNABio’s ribosome profiling services here.
Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer
Precision Oncology, 2024
Elisa De Paolis, Camilla Nero, Elisa Micarelli, Guido Leoni, Alessia Piermattei, Rita Trozzi, Elisa Scarselli, Anna Morena D’Alise, Luciano Giacò, Maria De Bonis, Alessia Preziosi, Gennaro Daniele, Diletta Piana, Tina Pasciuto, Gianfranco Zannoni, Angelo Minucci, Giovanni Scambia, Andrea Urbani, and Francesco Fanfani
This publication examines the potential for off-the-shelf neoantigen vaccines in mismatch repair–deficient (MMRd) endometrial cancer (EC). MMRd tumours accumulate insertions and deletions in microsatellite DNA, producing frameshift peptides (FSPs) that function as tumour-specific neoantigens (nAgs).
Using whole-exome sequencing and bespoke bioinformatics on 35 MMRd EC patient samples, the authors detected an average of 146 mutated mononucleotide repeats (MNRs), particularly enriched in cases with MLH1 deficiency. Comparative analysis with NOUS-209,a previously validated neoantigen vaccine, showed significant overlap, indicating many shared FSPs across patients. The researchers further confirmed translation of select FSPs using ribosome profiling, validating their expression as proteins and strengthening their candidacy for vaccination targets.
These findings underscore the feasibility of developing an “off-the-shelf” neoantigen vaccine for MMRd EC by targeting recurrent, shared FSPs. By demonstrating both recurrent presence and active translation of these neoantigens, the study offers a promising foundation for future vaccine-based immunotherapy in EC. Ultimately, this work paves the way for broader, population-wide neoantigen vaccine designs in microsatellite instability-driven cancers.
Learn more about EIRNABio’s ribosome profiling services here.
Circular RNA-encoded oncogenic PIAS1 variant blocks immunogenic ferroptosis by modulating the balance between SUMOylation and phosphorylation of STAT1
Molecular Cancer, 2024
Xin Zang, Xiao-Yu He, Cheng-Mei Xiao, Qing Lin, Meng-Yue Wang, Cheng-Yan Liu, Ling-Yi Kong, Zhong Chen and Yuan-Zheng Xia
This paper explores a novel mechanism by which tumours evade immune-mediated cell death. While immune checkpoint blockade (ICB) therapies like anti-PD-1 can induce ferroptosis,a form of immunogenic cell death,via interferon-γ (IFNγ) and STAT1 signalling, their effectiveness remains limited in many cancers. Here the authors, investigate the role of a peptide encoded by the circular RNA, circPIAS1, in modulating ferroptosis in melanoma.
They discovered that circPIAS1, elevated in melanoma, encodes a previously unannotated 108-amino acid peptide (circPIAS1-108aa). This peptide localizes to the nucleus and promotes tumour cell growth. Mechanistically, circPIAS1-108aa recruits the SUMO E3 ligase RanBP2 to STAT1, enhancing its SUMOylation and preventing IFNγ-induced STAT1 phosphorylation. As a result, the expression of ferroptosis regulators SLC7A11 and GPX4 is restored, blocking lipid peroxidation and ferroptotic cell death.
Importantly, combining circPIAS1 knockdown with PD-1 blockade significantly reduced tumour growth in mouse models, suggesting that circPIAS1-108aa undermines the efficacy of immunotherapy by shielding cancer cells from ferroptosis.
Their work reveals how a circRNA-encoded peptide can modulate post-translational signalling to suppress immunogenic cell death, offering a potential target to enhance the success of ICB therapies in resistant cancers.
Learn more about EIRNABio’s ribosome profiling services here.