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. find using rats as model organisms, that a set of circRNAs are involved in development of the CNS and spinal cord repair. Polysome profiling shows high ribosome association on a small subset of these circRNAs, suggesting they yield translational products.
  • Hu et al. find that circSPIRE1 is a protein encoding circular RNA using polysome profiling. This contributes to prostate cancer progression through stabilising LRP5 to enhance oncogenic signalling.
  • Shi et al. find through polysome profiling that osteosarcoma cells resist chemotherapy by repression of with the translation of ribosomal protein allowing prioritization of survival pathways.

Genome-wide profiling and functional characterization of circular RNAs in neural development and injury: insights from a rat model research

Cellular and Molecular Life Sciences, 2025

Yang, J., Jin, N., Zhang, S., Tan, Y., Chen, Z., Huang, X., Li, G., Yu, B., Shi, J., Gu, X. and Cui, Z.

Sunday Paper 1

It is understood that circular RNAs (circRNAs) have the potential to act as gene regulators in disease and are particularly active in the central nervous system (CNS). However, the expression of these in CNS development, especially in the spinal cord of mammals is poorly understood. This study used rats as model organisms to examine expression of circRNAs during CNS development and following spinal cord injuries.

The authors observed that circRNAs were significantly upregulated in CNS tissue compared to peripheral nervous system tissue. Expression levels were found to be low at early embryonic stages of spinal cord development but exhibited two expression peaks at later stages associated with key developmental events such as the rapid growth of the nervous system, neural tube closure, and accelerated neuron differentiation. In contrast to the general upregulation identified during spinal cord development, the authors noted that most differentially expressed circRNAs were downregulated in spinal cord injury (SCI).

Using polysome profiling, the authors observed that most circRNAs were not translated except for a small set that were enriched in the polysome fraction, suggesting they may be translated into functional proteins that play a role in neural development, differentiation and perhaps also in pathways of repair.

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

A novel polypeptide encoded by circSPIRE1 promotes prostate cancer proliferation and migration by restraining the ubiquitin-dependent degradation of LRP5

Journal of Experimental & Clinical Cancer Research, 2025

Hu, J., Shi, J., Wang, J., Xiao, Y., Kong, D., Gao, M., Luo, T., Xu, S., Yuan, Z., Ma, X. and Dong, X.

Sunday Paper 2

In this study, the authors characterize rtSPIRE1, a novel protein encoded by the circular RNA circSPIRE1, which they identified as a key contributing factor in prostate cancer progression.

Polysome profiling in this study showed that circSPIRE1 is enriched in polysome fractions indicating both active and robust translation instead of simply passive and non-protein coding ribosome association with the mRNA. To confirm these findings, both Western blotting and mass spectrometry testing show that the translated product of circSPIRE1 is present.

The authors show that rtSPIRE1 binds to and stabilises LRP5 which is involved in the Wnt/β-catenin signalling pathway that regulates cell growth and migration. This binding prevents the ubiquitin-mediated degradation of LRP5 thereby enhancing downstream oncogenic signalling pathways such as PI3K/AKT. This drives uncontrolled cell growth and migration leading to prostate cancer progression.

Overall, this study illustrates how polysome profiling can uncover the protein coding potential of circular RNAs such as circSPIRE1 to confirm their contribution to disease, demonstrating how this approach can help identify new biomarkers that may be targeted in treatments beyond conventional means.

Learn more about EIRNABio’s polysome profiling services here.

Chemotherapeutic drug-triggered AEP-cleaved G3BP1 orchestrates stress granules/nucleoli/mitochondria in osteosarcoma

Bone Research, 2025

Shi, Z., Zhao, J., Lv, Q., Liao, K., Cao, L., Yang, J., Wang, M., Zhou, L., Xu, H., Ge, J. and Qiu, Y.

Sunday Paper 3

This study investigates how osteosarcoma (OS) cells respond to cell stress caused by chemotherapy. Chemotherapy exposure activates a cysteine protease, asparagine endopeptidase (AEP) which causes cleavage of a stress granule protein, G3BP1. This causes stress granule assembly disruption causing rewiring of stress response pathways to promote cell survival. This form of G3BP1 alters the dynamics of stress granules promoting communication between the nucleus and mitochondria. This manipulation allows cells to resist the hostile environment that is created due to chemotherapy contributing to the poor prognosis and high recurrence of osteosarcoma.

This paper shows that activation of this pathway is initiated through translational control mechanisms. Through translational assays and polysome profiling, the authors of this study investigate how protein production in the OS cells is selectively programmed to prioritize resources and stress response pathways. Polysome profiling shows a reduction in association of polysomes with ribosomal protein encoding mRNAs in cells overexpressing AEP. As there is less binding of ribosomes to this mRNA, this suggests in this condition, OS cells globally repress translation. This means there will be less ribosomes in the cell to make proteins causing a downregulation in growth and protein production to prioritise survival during chemotherapy.

The findings of this study, offer an opportunity to investigate the potential for producing a therapeutic designed to block the enzymatic activity of APE which would prevent G3BP1 cleavage. If a drug such as this was developed it could be administered in tandem with chemotherapy to block chemotherapy resistance in OS cells.

Learn more about EIRNABio’s polysome profiling services here.