June 29th, 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,

  • Schwarzmueller et al. underscored the function of ribosome profiling analysis to distinguish functional lncRNAs from misannotated coding transcripts and to uncover their mechanisms.
  • Škapik et al. uncovered that colorectal cancer (CRC) cells rely on the eIF2B–p-eIF2α axis to selectively translate oncogenic transcripts, particularly those induced by APC loss.
  • Tian et al. revealed that PWP1 supports the translation of key mRNAs involved in DNA replication, mismatch repair, and cell proliferation in CRC.

Identifying colorectal cancer-specific vulnerabilities in the Wnt-driven long non-coding transcriptome

Gut, 2024

Schwarzmueller, L.J., Adam, R.S., Moreno, L.F., Nijman, L.E., Logiantara, A., Eleonora, S., Bril, O., Vromans, S., de Groot, N.E., Giugliano, F.P. and Stepanova, E.

This study comprehensively maps and functionally validates Wnt-regulated long non-coding RNAs (lncRNAs) in colorectal cancer (CRC). Through global run-on sequencing and β‑catenin perturbation, the authors identify a cohort of lncRNAs driven by aberrant Wnt signaling. They then apply CRISPR interference screens to assess which of these lncRNAs are essential for long-term CRC cell expansion.

Ribosome profiling reveals that several Wnt-regulated lncRNAs, including LINC02418, are non-coding yet closely associated with translational machinery, suggesting regulatory roles beyond protein-coding potential. LINC02418 sustains high levels of the oncogene MYC by acting as a competing endogenous RNA—sponging miR-24 to prevent MYC repression—and supports cancer stem cell properties while blocking differentiation. In xenograft CRC models, LINC02418-targeted siRNAs significantly suppresses tumor growth, demonstrating therapeutic potential.

In summary, the paper reveals how Wnt-driven lncRNAs like LINC02418 act as CRC-specific vulnerabilities and offers a promising siRNA-based strategy to target them, bypassing challenges of directly inhibiting Wnt signaling.

Learn more about EIRNA Bio’s ribosome profiling services here.

Maintenance of p-eIF2α levels by the eIF2B complex is vital for colorectal cancer

The EMBO Journal, 2025

Škapik, I.P., Giacomelli, C., Hahn, S., Deinlein, H., Gallant, P., Diebold, M., Biayna, J., Hendricks, A., Olimski, L., Otto, C. and Kastner, C.

This study reveals how colorectal cancer (CRC), particularly in APC-deficient contexts, exploits a delicate balance of translational control via phosphorylated eIF2α (p‑eIF2α) and the eIF2B complex. Surprisingly, despite elevated global protein synthesis, CRC cells show increased p‑eIF2α, which normally suppresses translation, and physical reliance on the decameric eIF2B complex to sense this phosphorylation.

Targeted knockdown or mutation of eIF2Bα and eIF2Bδ—key subunits responsible for sensing p‑eIF2α—disrupts this sensing mechanism, leading to reduced viability in CRC cell lines and APC‑mutant murine and patient organoids. Crucially, depleting eIF2Bα halts translation of growth-promoting transcripts upregulated by APC loss—without broadly suppressing protein synthesis—and selectively triggers cell cycle arrest rather than apoptosis, sparing normal cells and indicating a potential therapeutic window.

Ribosome profiling further confirms that the eIF2B/p‑eIF2α axis is essential for translating oncogenic mRNAs. The findings position the eIF2B‑p‑eIF2α interaction, especially via eIF2Bα, as a novel and actionable vulnerability in CRC.

Learn more about EIRNA Bio’s ribosome profiling services here.

Periodic tryptophan protein 1 promotes colorectal cancer growth via ribosome biogenesis

International Journal of Clinical Oncology, 2025

Tian, Y., Zhang, H., Xiang, Z., Xu, C., Xue, H. and Xu, Q.

The study investigates Periodic Tryptophan Protein 1 (PWP1)—a WD40-domain protein—as an oncogenic driver in colorectal cancer (CRC) via its role in ribosome biogenesis. Bioinformatic KEGG analysis highlighted PWP1 as overexpressed in CRC tissues and central to the ribosome synthesis pathway.

Functional assays in vitro and in vivo using orthotopic CRC mouse models reveal that PWP1 knockdown significantly impairs tumour growth. Immunofluorescence confirms reduced nascent rRNA synthesis upon PWP1 depletion, and polysome profiling shows decreased abundance of mRNAs tied to DNA replication and mismatch repair. Crucially, ribosome profiling demonstrates that these proliferation- and genomic maintenance–related transcripts are specifically downregulated at the translational level following PWP1 loss.

This indicates PWP1 acts as a regulator enabling efficient ribosome assembly, which in turn drives translation of key mRNAs essential for CRC cell division and genome stability. Overall, PWP1 emerges as a promising therapeutic target. Disrupting PWP1’s function selectively dampens ribosome biogenesis–dependent oncogenic processes and tumour growth in CRC.

Learn more about EIRNA Bio’s ribosome profiling and polysome profiling services here.

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