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,

  • Yang et al. showed that METTL5-driven rRNA methylation promotes prostate cancer by enhancing IRF7/DNA2 signaling to maintain mitochondrial function and prevent stress-induced mitophagy.
  • Zang et al. underlined that PUM1/2 promote translation of chromatin regulators during mammalian spermatogenesis.
  • Kan et al. showed that IGF2BP3 stabilizes and enhances translation of m⁶A-modified NLRP3 mRNA, promoting parathyroid hyperplasia and secondary hyperparathyroidism in CKD.

METTL5-mediated rRNA modification controls prostate cancer progression through the IRF7/DNA2 axis and mitophagy regulation

Oncogene, 2026

Yang, R., Ge, Q., Wu, F., Long, M., Li, B., Hong, Z., Xu, W., Guo, M., Feng, T., Tian, X., Zhang, W., Chang, K., Wan, F., Shang, Z., Wang, Z., Zhan, M., Xu, B. and Ye, D.

Sunday Paper 1

METTL5 functions as an oncogenic rRNA m⁶A methyltransferase that is progressively elevated in prostate cancer and associated with poor prognosis. METTL5 is upregulated in prostate cancer and methylates 18S rRNA at A1832, enhancing global translational output while selectively promoting the translation of specific targets like IRF7. Polysome profiling demonstrated that depleting METTL5 impairs translation initiation, evidenced by a markedly reduced active polysome fraction and decreased ribosome engagement on responsive transcripts like IRF7. This supports the finding that METTL5 enhances the selective translation of mRNAs harboring a specific GCACGN(2-4)CC motif within their 5′-untranslated region (5′-UTR).. Among these targets, IRF7 is preferentially translated and subsequently activates DNA2 transcription. DNA2 maintains mitochondrial DNA integrity and oxidative phosphorylation, thereby supporting prostate cancer cell survival and growth. Disruption of the METTL5–IRF7–DNA2 axis causes mitochondrial dysfunction, increased ROS, and compensatory mitophagy, ultimately inhibiting tumour growth. Importantly, METTL5 inhibition using locked nucleic acids suppressed prostate tumour growth in vivo without obvious systemic toxicity. Overall, the study links rRNA modification, selective translation, mitochondrial homeostasis, and mitophagy, identifying METTL5 as a potential therapeutic vulnerability in advanced prostate cancer.

Learn more about EIRNABio’s polysome profiling services here.

PUM1 and PUM2 promote translation of chromatin regulators to ensure mammalian spermatogenesis

Science Advances, 2026.

Zang, M., Liu, S., Xie, Z., Yang, D., Wang, K., Ding, Y., Zhu, T., Zhang, S., Zhao, T., Yao, B., Liu, M., Lin, K. and Xu, E.Y.

Sunday Paper 2

This paper shows that PUM1 and PUM2 act as translational activators in mouse germ cells, promoting expression of chromatin regulators such as SUZ12, SIN3A, JARID2, and SMARCA5. Loss of both proteins causes reduced translation, defective chromatin remodeling, impaired histone-to-protamine exchange, abnormal sperm development, and male sterility. Mechanistically, PUM1/2 cooperate with DAZL and PABPC1 to enhance protein production without substantially altering target mRNA stability.

Polysome profiling and ribosome sequencing (Ribo-seq) provided direct evidence for this translational role: PUM1/2 deficiency reduced the association of their target chromatin-regulator mRNAs with heavy polysomes, while Ribo-seq revealed widespread reductions in translation efficiency (TE) across these targets, all despite relatively stable mRNA levels.. Thus, the combination of these techniques  was crucial in demonstrating that PUM1/2 promote spermatogenesis primarily through translational activation, linking RNA regulation to chromatin organization.

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

IGF2BP3 mediates the mRNA upregulation of NLRP3 to promote parathyroid cell proliferation in chronic kidney disease via an m⁶A-dependent manner

Endocrine, 2026.

Kan, S., Zhao, B., Miao, L., Han, Z., Li, Q., Wu, Y. and Wang, L.

Sunday Paper 3

IGF2BP3 acts as a key regulator of parathyroid hyperplasia in chronic kidney disease (CKD)–associated secondary hyperparathyroidism. IGF2BP3 is elevated in hyperplastic parathyroid tissue and promotes NLRP3 expression through an m⁶A-dependent mechanism. By binding m⁶A-modified NLRP3 mRNA, IGF2BP3 increases both its stability and translation, enhancing NLRP3 protein production and promoting parathyroid cell proliferation. Knockdown of either IGF2BP3 or NLRP3 reduced parathyroid hyperplasia and PTH levels in a CKD/secondary hyperparathyroidism rat model. Importantly, polysome profiling demonstrated that IGF2BP3 increases the association of NLRP3 mRNA with actively translating polysomes, providing direct evidence that IGF2BP3 regulates NLRP3 at the translational level, in addition to stabilizing its transcript. NLRP3 overexpression rescued the effects of IGF2BP3 depletion, supporting the IGF2BP3–NLRP3 axis as a potential therapeutic target for CKD-associated parathyroid hyperplasia.

Learn more about EIRNABio’s polysome profiling services here.