August 17th, 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,

  • Challa et al. highlight that MARylation of ribosomal protein RACK1 functions as a key regulator of stress granule formation.
  • Kellett et al. study that Focal Adhesion Kinase (FAK) acts as a driver of ribosome biogenesis and is a promising therapeutic target in advanced thyroid cancer.

  • Liu et al. identify that the NAT10-ACOT7 axis acts to reprogram fatty acid metabolism, suppress ferroptosis, and promote ovarian cancer progression.

RACK1 MARylation regulates translation and stress granules in ovarian cancer cells

Journal of Cell Biology, 2025

Challa, S., Nandu, T., Kim, H.B., Gong, X., Renshaw, C.W., Li, W.C., Tan, X., Aljardali, M.W., Camacho, C.V., Chen, J. and Kraus, W.L.

The authors identify mono-ADP-ribosylation (MARylation) of the ribosomal protein RACK1 at residues Asp144, Glu145, and Asp203 by PARP14 as a key regulator of stress granule dynamics and translation. MARylation promotes RACK1’s localization to stress granules alongside proteins like G3BP1 and eIF3η, while the hydrolase TARG1 removes MARylation to enable stress granule disassembly and translation recovery.

Using ribosome profiling, Challa et al. found that in OVCAR3 cells with MARylation-deficient RACK1, there was selectively reduced translation of transcripts linked to ovarian cancer progression, including AKT1 and DNA repair genes. Polysome profiling analysis revealed that MARylation is not required for RACK1’s ribosome binding but is essential for recruiting G3BP1 to ribosomes, linking translation machinery to stress granule formation.

In conclusion, the study uncovers a molecular switch integrating translation control, stress response, and cancer-related pathways, with implications for targeting RACK1 MARylation in ovarian cancer therapy.

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

Focal adhesion kinase promotes ribosome biogenesis to drive advanced thyroid cancer cell growth and survival

Frontiers in Oncology, 2025

Kellett, M.D., Sharma, V., Sherlock, M.E., Pugazhenthi, U., Rose, M.M., Joshi, M.U., Dzieciatkowska, M., Nguyen, V., Reigan, P., Hansen, K.C.,Kieft, J.S., and Schweppe, R.E.

Kellett et al. unveil a novel nucleolar function for Focal Adhesion Kinase (FAK). In aggressive thyroid cancers, autophosphorylated FAK at Tyr-397 (pY397) accumulates in the nucleolus, a hub for ribosomal RNA synthesis and ribosome assembly. This nucleolar localization depends on FAK’s kinase activity and on nucleophosmin 1 (NPM1).

Functionally, nuclear/nucleolar FAK is essential for anchorage-independent growth, and its depletion reduces overall protein synthesis—specifically impairing the 60S ribosomal subunit. Proteomic BioID analysis identified interactions between pY397-FAK and nucleolar ribosome biogenesis factors like NOP56, a core component of snoRNPs required for 60S maturation.

These findings position nucleolar FAK as a driver of ribosome biogenesis and a promising therapeutic target in advanced thyroid cancer.

Learn more about EIRNABio’s polysome profiling services here.

m6A-driven NAT10 translation facilitates fatty acid metabolic rewiring to suppress ferroptosis and promote ovarian tumorigenesis through enhancing ACOT7 mRNA acetylation

Oncogene, 2024.

Liu, Y., Li, J., Xu, J., Long, Y., Wang, Y., Liu, X., Hu, J., Wei, Q., Luo, Q., Luo, F., Qin, F., Yi, Q., Yang, Y., Dang, Y., Xu, J., Liu, T. and Yi, P.

N-acetyltransferase 10 (NAT10) is markedly upregulated in ovarian cancer and correlates with poor prognosis. Through polysome profiling analysis, NAT10 translation is enhanced by the m6A-reader IGF2BP1 in an m6A-dependent manner. NAT10 then installs N4-acetylcytidine (ac4C) on ACOT7 mRNA, boosting its stability and translation. When NAT10 was silenced or inhibited, ACOT7 mRNA shifted from heavy to light polysome fractions, indicating reduced translational efficiency.

Elevated ACOT7 levels reprogram fatty acid metabolism, suppressing ferroptosis—an iron-dependent form of cell death—and thereby support tumour growth. Notably, the FDA-approved drug fludarabine targets NAT10, reducing ac4C modifications on ACOT7 mRNA and effectively suppressing ovarian tumour progression in both cell-derived xenograft and patient-derived organoid models.

Learn more about EIRNABio’s polysome profiling service here.

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