
March 2nd, 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,
- Kohvakka et al. demonstrated polysome profiling to reveal that moderating EPCART lncRNA could influence the translation of PCa-associated mRNAs without altering global translation levels.
- Chatterjee et al. employed polysome profiling to show that the loss of PKCλ/ι during enzalutamide treatment causes EZH2 to promote a resistance program against TGFβ.
- Bertrand et al. used ribosome profiling to discover the potential role of alternative open reading frame-encoded peptides as T cell antigens for immunotherapies.
Long noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer
Cancer Gene Therapy, 2024
Kohvakka, A., Sattari, M., Nättinen, J., Aapola, U., Gregorová, P., Tammela, T.L., Uusitalo, H., Sarin, L.P., Visakorpi, T. and Latonen, L.
In this paper, the authors investigated the role of long noncoding RNA (lncRNA) in prostate cancer (PCa). EPCART (ERG-positive PC-associated androgen responsive transcript) is a PCa-related lncRNA that was discovered to impact PCa tumour progression in vitro.
Kohvakka et al. employed polysome profiling to assess the impact of EPCART on global translation. They found that knocking out EPCART did not lead to significant changes in overall translation rates, as EPCART did not code for proteins. Nonetheless, EPCART was predominantly located in the cytoplasm and associated with translation sites, suggesting a role in modulating specific translational processes of PCa cells rather than affecting global protein synthesis.
Knocking out EPCART upregulated the levels of PDCD4, a translation inhibitor. This led to reduced activation of the AKT pathway and mTORC1 inhibition, both crucial for protein synthesis. This suggests that EPCART promotes translation in PCa cells by modulating the PI3K/AKT/mTORC1 signalling pathway and suppressing PDCD4, influencing cancer progression without significantly affecting global protein synthesis.
Learn more about EIRNA Bio’s polysome profiling service here.
Increased translation driven by non-canonical EZH2 creates a synthetic vulnerability in enzalutamide-resistant prostate cancer
Nature Communications, 2024
Chatterjee, S.S., Linares, J.F., Cid-Diaz, T., Duran, A., Khan, M.I.K., Osrodek, M., Brady, N.J., Reina-Campos, M., Marzio, A., Venkadakrishnan, V.B., Bakht, M.K., Khani, F., Mosquera, J.M., Robinson, B.D., Moyer, J., Elemento, O., Hsieh, A.C., Goodrich, D.W., Rickman, D.S., Beltran, H., Moscat, J. And Diaz-Meco, M.T.
The authors investigated mechanisms behind therapy resistance in castration-resistant prostate cancer (CRPC), particularly focusing on the role of enhancer of zeste homolog 2 (EZH2).
Chatterjee et al. found that the protein kinase PKCλ/ι normally phosphorylates EZH2, leading to its degradation and maintaining its role within the canonical polycomb repressive complex 2 (PRC2). However, loss of PKCλ/ι during enzalutamide treatment causes EZH2 to adopt a non-canonical function, activating genes involved in protein synthesis and inducing a resistance program against transforming growth factor β (TGFβ).
This shift results in increased reliance on protein synthesis in PKCλ/ι-deficient CRPC cells, creating a synthetic vulnerability. Targeting this vulnerability could offer a new therapeutic strategy for overcoming enzalutamide resistance in prostate cancer.
Learn more about EIRNA Bio’s polysome profiling service here.
Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling
Nature Communications, 2025
Bertrand, L., Nelde, A., Ramirez, B.C., Hatin, I., Arbes, H., François, P., Demais, S., Labaronne, E., Decimo, D., Guiguettaz, L. and Grégoire, S.
Bertrand et al. employed ribosome profiling (Ribo-Seq) to map the translatome of HIV-1 in infected CD4+ T cells. Beyond the known viral protein-coding sequences, the authors identified 98 alternative open reading frames (ARFs), including small open reading frames (sORFs) located throughout the HIV genome, even in untranslated regions.
The study demonstrated that some of these ARF-encoded peptides are presented by MHC class I molecules and recognized by CD8+ T cells, indicating their potential role as T cell antigens. This suggested that these newly identified peptides could serve as novel immune targets, potentially improving HIV vaccine strategies and immunotherapies. The conservation of these ORFs across HIV-1 subtypes indicated their evolutionary importance, making them promising candidates for broad-spectrum antiviral interventions.
These findings expanded the understanding of the HIV-1 coding landscape and highlighted novel targets for immune recognition, which could inform future vaccine development strategies.
Learn more about EIRNA Bio’s ribosome profiling services here.