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,

  • Sheinberger et al. used high-throughput screening to identify compounds that drive MYC mRNA into stress granules, with ribosome profiling confirming that this mechanism significantly reduces MYC translation.
  • Postnivoka et al. find that growth medium composition influences RPE65 expression in ARPE-19 cells, primarily through transcriptional control.
  • Schibler et al. find through Ribo-seq that fluctuations of liver morphology based on circadian rhythms are associated with translational control, reflected in rhythmic protein production and ribosome loading.

Discovery of Small Molecules That Inhibit MYC mRNA Translation Through hnRNPK and Induction of Stress Granule-Mediated mRNA Relocalization

International Journal of Molecular Sciences, 2025.

Sheinberger, Y., Wassermann, R., Khier, J., Kassa, E., Vaturi, L., Slonim, N., Tverskoi, A., Mandaby, A., Demishtein, A., Klepfish, M., Shapira-Lots, I., and Alroy, I.

Sunday Paper 1

MYC is a potent oncogene in non-small cell lung carcinoma (NSCLC) where it is often overexpressed causing uncontrolled cellular proliferation. Through transcriptional and translational analysis, it is understood that there are often higher levels of the MYC protein in NSCLC cells than would be expected based on MYC mRNA abundancy, suggesting translational control.

The investigators of this study used high throughput screening of thousands of compounds to identify candidates that suppress MYC expression at the translational level , ultimately developing an optimized lead candidate named CMP76. This compound reduces MYC translation by promoting relocalisation of MYC mRNA to stress granules (SG) where translation is silenced. The RNA binding protein hnRNPK was identified as the primary target of CMP76. While normally predominantly nuclear, CMP76 treatment alters its function and causes it to translocate to the cytoplasm, where it co-localizes with MYC mRNA inside SGs.

This study used both RNA-seq and ribosome profiling to investigate transcript abundance and ribosome occupancy on MYC mRNA respectively. Using the screen’s top hit, CMP16, the key translatomic finding of this study is that treatment of the NSCLC cells with CMP16 significantly reduced the amount of ribosome footprints on MYC mRNA which in turn resulted in less MYC protein translation. Interestingly, there was no comparable reduction in the abundance of MYC mRNA transcripts. Overall, this demonstrates how translational control has the potential to selectively suppress oncogenes such as MYC which may be utilised as a drug target for treatment of NSCLC and other cancers.

Learn more about EIRNABio’s ribosome profiling services here.

Regulation of RPE65 expression in human retinal pigment epithelium cells

Scientific Reports, 2025.

Postnikova, O.A., William, S., Uppal, S., Bernstein, S.L., Poliakov, E., Rogozin, I.B. and Redmond, T.M.

Sunday Paper 2

RPE65 is a gene that encodes a critical enzyme in the visual cycle required to regenerate the light-sensitive chromophore. The RPE65 protein is mainly expressed in the retinal pigment epithelium (RPE) to support photoreceptors in the retina. It forms 11-cis-retinal, which combines with rods and cones to form visual pigments, such as rhodopsin, which allow photoreceptors to respond to light. Therefore, mutations in this gene that disrupt chromophore regeneration cause diseases such as Leber Congenital Amaurosis, leading to vision loss.

Using RNA-seq, the authors of the paper compared native RPE with cultured RPE models using the ARPE-19 cell line. It was found that RPE65 mRNA was expressed at much lower levels in cultured cells than in native tissue. Interestingly, ARPE-19 cells cultured in nicotinamide (NAM) medium instead of pyruvate (PYR) medium showed a much higher level of RPE65 mRNA and protein. This indicates that the medium in which the cells grow and metabolise strongly influences transcription of the RPE65 gene.

Investigators used polysome profiling, followed by qRT-PCR, to monitor the distribution of RPE65 mRNA across sucrose gradients and determine its ribosomal association.. The results found that there was no significant difference in RPE65 mRNA distribution in polysomes in ARPE-19 cells in either NAM or PYR conditions even though there was a difference in total RPE65 protein expression.  This suggests that the increase in RPE65 protein in the NAM medium condition is not due to increased translation but rather to transcriptional control.

Learn more about EIRNABio’s polysome profiling services here.

Daily liver rhythms: Coupling morphological and molecular oscillations

Proceedings of the National Academy of Sciences, 2025.

Schibler, U., Sinturel, F., Naef, F., Gerber, A. and Gatfield, D.

Sunday Paper 3

This study investigates how circadian rhythms regulate fluctuations in liver mass and morphology, and protein synthesis. The mass of the liver fluctuates between approximately 30 and 40% in mice and the findings of this paper suggest that the fluctuations are linked to variation in ribosome abundance and global protein synthesis.  The authors of this paper suggest that the liver’s capacity to make proteins changes throughout the day because the number of available ribosomes changes throughout the day. Even though there may be sufficient mRNA available, variation in ribosome availability can modulate how efficiently mRNAs are translated.

The liver is one of the most metabolically active organs and reactive oxygen species (ROS) are heavily produced as a byproduct of metabolism. However, ROS are known to damage DNA, protein and ribosomes thereby inhibiting protein synthesis. According to this study, the oscillation of ribosome and protein accumulation throughout the day in hepatocytes may may contribute to the renewal of cellular components.

Ribosome profiling showed that translational activity is not only a reflection of mRNA abundance but also  that many mRNA transcripts exhibit time-of-day–dependent ribosome occupancy, indicating circadian rhythms play a role in the regulation of translation in the liver. Ribo-seq data was particularly important for demonstrating that rhythmic protein production correlates strongly with ribosome loading and is associated with changes in ribosome abundance.. This evidence from ribosome profiling supports the hypothesis that translational control contributes substantially to liver physiology rather than transcriptional control alone.

Learn more about EIRNABio’s ribosome profiling services here.