Translatomics for ALS, testes and METTL1
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. showed that ribosomal protein RPS29 downregulation selectively reduces translation of key motor neuron proteins.
- Guo et al. identified stage-specific translational regulation in pathways essential for testicular development.
- Hu et al. revealed the mechanistic connection between tRNA modifications and translational control.
Machine learning-based proteomics profiling of ALS identifies downregulation of RPS29 that maintains protein homeostasis and STMN2 level
Communications Biology, 2025.
Xu, W., Guo, Z., Guan, Y., Lv, S., Gao, X., Luo, W., Cheng, T., Shao, Z., Tao, B., Wang, T. and Qiu, Z.
The authors developed an integrative pipeline combining machine learning, consensus clustering, proteomics, and validation to analyze a multi‑omics dataset from the Answer ALS (AALS) cohort. They profiled motor neurons derived from > 200 iPSC lines, quantifying ~4,400 proteins per sample. Classical differential‑expression analysis failed to uncover robust ALS‑associated proteins due to heterogeneity; instead, machine‑learning models identified a set of 110 candidate proteins that classify ALS vs controls.
Cross-referencing these candidates with proteomics from postmortem ALS motor neurons prioritized the ribosomal protein RPS29, which was consistently downregulated. Ribo‑seq could clarify how RPS29 downregulation selectively reduces translation of key motor neuron proteins. Functional assays revealed that loss of RPS29 reduces global protein synthesis, disrupts protein homeostasis (increased ubiquitylation), and impairs neuronal viability.
Importantly, RPS29 downregulation decreased translation of key motor‑neuron proteins, notably STMN2 — essential for axon maintenance and implicated in ALS pathology — and simultaneously enhanced aberrant repeat‑associated (RAN) translation of toxic peptides from expanded repeat mutations.
Thus, the study reveals a novel translational‑level mechanism: reduced RPS29 undermines normal protein synthesis (especially STMN2), promotes pathological translation, and contributes to motor‑neuron vulnerability, highlighting RPS29 as a potential therapeutic target.
Learn more about EIRNABio’s ribosome profiling services here.
Ribosome profiling sequencing reveals translational dynamics during yak testicular development
International Journal of Biological Macromolecules, 2025.
Guo, S., Cao, M., Wang, X., Ding, Z., Kang, Y., Hu, L., Zhang, B., Pei, J. and Guo, X.
The authors used ribosome profiling (Ribo‑seq) alongside RNA‑seq to map the translational landscape of testes from Bos grunniens (yak) at three developmental stages: 6‑month (Y6M), 18‑month (Y18M), and 4‑year (Y4Y). They found that ribosome‑footprint features in yak testis mirror those observed in other mammals. Genes with differential translation during sexual maturation were enriched in pathways central to spermatogenesis and testicular development, including meiotic cell cycle, PI3K‑Akt, and Notch signaling.
Between 6 M and 18 M, many genes displayed discordant changes in transcription versus translation efficiency, suggesting post‑transcriptional regulation possibly linked to protein ubiquitination. From 18 M to 4 Y, translational changes occurred without corresponding mRNA changes, implicating processes such as acetyltransferase and phosphotransferase activity. Protein–protein interaction analysis highlighted potential stage‑specific regulatory genes. Moreover, the study identified 106 novel small open reading frames (sORFs) with translational potential — expanding the repertoire of peptides potentially relevant for testicular biology.
In summary, this work reveals a highly dynamic, stage‑specific translational regulation landscape during yak testis development, underscoring the importance of translational control — beyond mRNA levels — in spermatogenesis and male reproductive maturation.
Learn more about EIRNABio’s ribosome profiling services here.
METTL1 promotes cadmium-induced stress granules formation via enhancing translation of G3BP1 and expression of m7G-3'tiRNA MetCAT
Cell Biology and Toxicology, 2025.
Hu, W., Liang, Y., Ying, X., Huang, Y., Xiong, C., Liu, B., Lv, Y., Chen, C., Zhang, C., Zhang, H., Li, H., Yang, M., and Ji, W.
The study investigates how METTL1 — a known methyltransferase that installs N⁷‑methylguanosine (m⁷G) modifications on tRNAs — contributes to cellular stress responses under cadmium exposure. The authors demonstrate that exposure to CdCl₂ induces formation of stress granules (SGs) in urothelial and bladder cancer cells, and that METTL1 strongly promotes this SG assembly.
Through ribosome profiling technique, it detects that METTL1 enhances the translation of the SG‑core protein G3BP1: although G3BP1 mRNA levels remain unchanged, METTL1 up‑regulation increases its polysome association and protein abundance. METTL1 increases expression of a newly identified m⁷G‑modified tRNA‑derived fragment, the 3′ tiRNA from Met‑tRNA. This modified tiRNA itself facilitates SG formation. Both elevated G3BP1 protein and higher mtiRM levels cooperate to drive SG assembly under cadmium stress.
The authors propose that this dual role of METTL1 — modulating translation via tRNA methylation and generating functional tiRNAs — links epitranscriptomic regulation to stress granule dynamics and potentially to the cellular changes involved in cadmium‑related carcinogenesis.
Learn more about EIRNABio’s ribosome profiling services here.
