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,

  • Li et al. discovered stress-induced UFD1s microprotein that rewires ubiquitination of UFD1f and IPMK, promoting adaptive metabolism and protecting against disease
  • Liu et al. revealed how RNA modifications influence protein synthesis by linking NCIN capping to translation efficiency.
  • Yang et al. identified key inflammatory and metabolic genes, cellular interactions, and potential therapeutic targets for treatment.

A UFD1 variant encoding a microprotein modulates UFD1f and IPMK ubiquitination to play pivotal roles in anti-stress responses

Nature Communications. 2025

Li, X., Wang, X., Liu, X., Shan, G. and Chen, L

Sunday Paper 1

Ribosome profiling identifies UFD1s, a conserved stress-responsive mRNA isoform of the UFD1 gene that encodes a previously unrecognized microprotein with key roles in cellular stress adaptation. UFD1s modulates protein ubiquitination by competitively binding the E3 ligase MARCH7, thereby reducing K63-linked ubiquitination of the full-length UFD1 protein (UFD1f). This alters ubiquitination dynamics, a central mechanism in stress responses.

A major downstream target is IPMK (inositol polyphosphate multikinase), whose K48- and K11-linked ubiquitination increases, leading to its destabilization. Through this regulation, UFD1s enhances autophagy and fatty acid oxidation, helping cells adapt metabolically to stress. Functionally, loss of UFD1s in mice causes metabolic dysfunction and accelerated progression of nonalcoholic steatohepatitis (NASH), highlighting its physiological importance. Conversely, restoring UFD1s expression (via plasmid or circRNA) alleviates disease symptoms, suggesting therapeutic potential.

Overall, the paper reveals that a small, previously overlooked microprotein can coordinate ubiquitination and metabolic pathways to maintain cellular homeostasis under stress, expanding understanding of stress-response regulation and microprotein biology.

Learn more about EIRNABio’s ribosome profiling services here.

CompasSeq: epitranscriptome-wide percentage assessment of metabolite-capped RNA at the transcript resolution

Nature Communications. 2025

Liu, Y., Li, D., Wang, X., Niu, K., Bai, J., Qu, L. and Liu, N

 

Sunday Paper 2

This study introduces CompasSeq, a combined experimental and computational platform designed to quantify metabolite-capped RNAs (NCIN-RNAs) across the transcriptome with transcript-level resolution. Unlike prior methods that detect only specific caps (e.g., NAD), CompasSeq enables global, quantitative measurement of the proportion of metabolite-capped versus canonical m⁷G-capped RNAs. Ribosome profiling (Ribo-seq) helps show that changes in metabolite capping can alter translation output without corresponding changes in transcript levels, highlighting a new regulatory layer controlling gene expression.

The method uses selective enzymatic decapping, adapter ligation, and spike-in controls to accurately capture NCIN-capped RNAs and calculate their stoichiometry. An accompanying computational pipeline applies normalization and statistical modelling to infer capping percentages per transcript. Applying CompasSeq to mouse liver, the authors show that ~45% of transcripts carry metabolite caps, typically at 5–30% levels, indicating these modifications are widespread and biologically significant. They also uncover age-associated changes in metabolite capping, and notably, a disconnect between RNA expression levels and capping status, suggesting an additional regulatory layer beyond transcription.

Overall, CompasSeq provides the first epitranscriptome-wide quantitative framework for studying metabolite-capped RNAs, enabling deeper investigation into their roles in gene regulation and cellular physiology.

Learn more about EIRNABio’s ribosome profiling services here.

Identification and Mechanistic Studies of Key Genes in Thalamic Hemorrhage Pain by Multi-omics

Journal of Integrative Neuroscience. 2025

Yang, C., Gao, J., Li, Y., Xiao, Y. and Huang, T

Sunday Paper 3

This study employed a multi-omics approach to investigate the molecular mechanisms underlying thalamic hemorrhage pain (THP) using a validated mouse model. The researchers integrated transcriptomics, proteomics, metabolomics, ribosome profiling, and single-cell RNA sequencing to identify genes and pathways associated with the condition.

By combining these datasets, they detected differentially expressed genes, proteins, ribosome-associated transcripts, and metabolites, and intersected them with single-cell data to pinpoint key regulatory genes. Eight hub genes, including Ftl1, Tpm4, Ccl3, Ccl4, Ccr2, Il33, Cxcl2, and Ly6c2, were identified as central to THP pathogenesis. These genes are mainly involved in inflammatory signaling, oxidative phosphorylation, and ribosomal function.

Single-cell analysis further revealed specific cell populations and their interactions, providing insight into cellular communication and disease progression. The study also highlighted potential therapeutic candidates through drug prediction analysis. Overall, it uncovers key molecular networks driving THP and suggests targets for future treatment strategies.

Learn more about EIRNABio’s ribosome profiling services here.