August 3rd, 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,
- Xu et al. identify that a LINC00472-derived micropeptide suppresses non‑small cell lung cancer (NSCLC) proliferation and migration by disrupting HDAC2/SP1 interaction.
- Nah et al. show that microprotein SMIM26 enables serine-dependent mitochondrial translation of complex subunit ND5.
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Ely et al. explore a novel set of antigens unique to pancreatic tumours that can be recognised by T cells.
A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells
Cancer Cell International, 2025
Xu, L., Kuang, H., Peng, H., Wu, S., Bai, Y., Jia, X. and Yao, W.
This study reveals that the long non‑coding RNA LINC00472 encodes a 15‑amino‑acid micro‑polypeptide (LINC00472‑ORF) with potent tumour‑suppressive effects in non‑small cell lung cancer (NSCLC). A multi‑omics strategy—integrating ribosome profiling (ribo-seq), transcriptomics, and protein co‑expression analysis—identified and validated this small peptide using TRAP, Western blotting, and immunofluorescence.
In this study, ribo-seq was instrumental in providing direct evidence of active translation from a small open reading frame (sORF) within LINC00472, challenging the conventional view that such transcripts are noncoding. This technique enabled precise mapping of ribosome-protected fragments, confirming translational activity and guiding further validation.
Functional assays showed that expression of LINC00472‑ORF significantly inhibits NSCLC cell proliferation, migration, invasion in vitro and suppresses tumour growth in xenograft models. LINC00472‑ORF disrupts the interaction between HDAC2 and SP1, leading to SP1 hyperacetylation, cytoplasmic sequestration, and transcriptional repression of oncogenic SP1 targets. This highlights a novel epigenetic‑transcriptional mechanism via a lncRNA‑derived micro‑peptide with potential therapeutic implications in NSCLC.
Learn more about EIRNABio’s ribosome profiling service here.
Microprotein SMIM26 drives oxidative metabolism via serine-responsive mitochondrial translation
Molecular Cell, 2025
Nah, J., Mahendran, S., Kerouanton, B., Cui, L., Hock, D.H., Cabrera-Orefice, A., Dunlap, K., Robinson, D., Tung, D.W., Leong, S.H. and Tan, K.Y.
A microprotein encoded by LINC00493 known as SMIM26 is identified as a critical regulator of mitochondrial oxidative metabolism. Ribosome profiling (ribo-seq) demonstrates that microprotein SMIM26 regulates serine-responsive mitochondrial translation. SMIM26 scaffolds mitochondrial serine transporters SFXN1/SFXN2 and the mitoribosome, forming a functional complex that enables serine-dependent translation of the complex I subunit mt-ND5.
Loss of SMIM26 impairs serine import, disrupts folate metabolism and mitochondrial tRNA modifications (τm⁵U and τm⁵s²U), causing ND5 translation failure and complex I deficiency. It is found that SMIM26 impairs tumour growth in folate‑dependent leukemia xenografts. The work uncovers a metabolite‑gated mechanism where nutrient availability controls localized mitochondrial translation—positioning SMIM26 as a pivotal integrator of one‑carbon flux, respiratory chain assembly, and oxidative phosphorylation.
Learn more about EIRNABio’s ribosome profiling service here.
Pancreatic cancer–restricted cryptic antigens are targets for T cell recognition
Science, 2025
Ely, Z.A., Kulstad, Z.J., Gunaydin, G., Addepalli, S., Verzani, E.K., Casarrubios, M., Clauser, K.R., Wang, X., Lippincott, I.E., Louvet, C. and Schmitt, T.
Ely et al. investigates cryptic antigens, which are peptides derived from noncoding or normally untranslated genomic regions. The antigens are uniquely presented by HLA class I molecules on pancreatic ductal adenocarcinoma (PDAC) cells.
Using immunopeptidomics and mass spectrometry, the researchers identified multiple cryptic peptides restricted to pancreatic tumours. Crucially, many of these cryptic antigens elicited robust CD8⁺ T cell responses when tested ex vivo with autologous T cells. These findings expand the pool of potential tumour-specific targets beyond classical neoantigens derived from mutations.
Ribo-seq reveals active translation of genomic regions previously considered noncoding. These regions give rise to cryptic peptides that are not predicted by conventional gene annotations. Ribo-seq also provides direct evidence that these cryptic peptides are not merely theoretical but are actively synthesized in tumour cells.
By demonstrating that cryptic peptides can be naturally presented and recognized by tumour‑infiltrating or peripheral T cells, the work points to a new class of immunogenic targets for PDAC immunotherapy and vaccine development.
Learn more about EIRNABio’s ribosome profiling service here.