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,

  • Rana, A. and Thakur, A. demonstrate that translational regulation drives stress adaptation and pathogenesis in Candida glabrata, showing that Gcn2-mediated eIF2α phosphorylation downregulates global translation to activate Gcn4-dependent survival pathways under nutrient and oxidative stress.
  • Yu, Z. et al. reveal that the RNA-binding E3 ligase MKRN2 selectively restrains inflammation, demonstrating that MKRN2 binds Il6 mRNA and ubiquitinates PAIP1 to disrupt its interaction with eIF4A and suppress Il6 translational efficiency.
  • Rajan, K.S. et al. show that a stage-specific snoRNA dictates specialized ribosome function in Leishmania, using polysome profiling and polysome-seq to demonstrate how rRNA structural remodelling selectively rewires mRNA translation.

Translation regulation promotes stress adaptation in the human fungal pathogen Candida glabrata

Genetics, 2025

Rana, A. and Thakur, A.

Sunday Paper 1

Candida glabrata is an opportunistic human fungal pathogen whose clinical importance is increasing because of its ability to tolerate host-associated stresses and resist antifungal treatment. C. glabrata lacks true hyphal formation and relies heavily on robust environmental stress adaptation to survive host immune defences. During macrophage engulfment, C. glabrata encounters severe oxidative stress and nutrient deprivation. Understanding the post-transcriptional mechanisms that orchestrate fungal survival under these harsh microenvironments is critical for identifying novel antifungal targets.

Rana and Thakur demonstrate that C. glabrata employs rapid translational reprogramming to survive oxidative stress and amino acid starvation. Under stress conditions, the C. glabrata kinase Gcn2 phosphorylates eukaryotic initiation factor 2α (“eIF2” α), triggering an immediate suppression of it’s own global protein translation initiation, shown using polysome profiling. This global translational shutdown allows the fungus to conserve metabolic energy and facilitates its selective translational and transcriptional activation of Gcn4, a master transcriptional regulator. Activated Gcn4 coordinates a specialized gene expression program that detoxifies reactive oxygen species (ROS) and restores metabolic homeostasis. Deletion mutants (Δgcn2 and Δgcn4) exhibit unchecked ROS accumulation, severe growth impairment under nutrient stress, and compromised replication within human host macrophages, leading to attenuated virulence in mice.

This work highlights translational control as a major driver of fungal pathogenesis. The study establishes the Gcn2-Gcn4 translational axis as a potential target for antifungal therapeutic development.

Learn more about EIRNABio’s polysome profiling services here.

The RNA-binding E3 ligase MKRN2 selectively disrupts IL6 translation to restrain inflammation

Nature Immunology, 2025

Yu, Z., Li, X., Huang, J., Pan, J., Cheng, J., Liu, P., Yang, M., Chen, T., Zhang, Q., Zhou, Y. and Wu, J.

Sunday Paper 2

Dysregulated production of pro-inflammatory cytokines like interleukin-6 (IL-6) drives severe tissue damage in autoimmune and inflammatory diseases. While transcription factors regulating Il6 gene induction are well defined, the post-transcriptional mechanisms that selectively restrict IL-6 protein synthesis remain incompletely understood. Identifying factors that specifically tune Il6 translation without causing broad translational suppression offers vital strategies for anti-inflammatory therapies.

This study identified Makorin Ring Finger Protein 2 (MKRN2) as an RNA-binding E3 ubiquitin ligase that selectively represses IL-6 production in activated macrophages. Macrophage-specific Mkrn2 knockout mice exhibited elevated serum IL-6 levels and heightened susceptibility to dextran sodium sulfate-induced colitis. Unexpectedly, MKRN2 deficiency did not alter Il6 transcript levels or mRNA stability. To resolve how MKRN2 restricts IL-6 synthesis, the authors performed polysome profiling. Polysome profiling revealed that MKRN2 loss shifts Il6 mRNA from translationally inactive sub-polysomal fractions into heavy, translationally active polysomes without altering global translation. Mechanistically, MKRN2 binds directly to Il6 mRNA and catalyzes K29-linked polyubiquitination of the translation initiation coactivator PAIP1, disrupting its interaction with eIF4A to selectively block Il6 translation initiation.

This study highlights polysome profiling as the key translatomics assay that uncoupled mRNA stability from translational efficiency. Through this technique direct proof was provided that MKRN2 functions as a gene-specific translational brake, revealing a novel post-transcriptional checkpoint that regulates cytokine storms and autoimmune pathology.

Learn more about EIRNABio’s polysome profiling services here.

A small nucleolar RNA dictates the structure and function of translating ribosomes in Leishmania

Nature Communications, 2026

Rajan, K.S., Aryal, S., Murugeshan, S., Zhu, Y., Bashan, A., Olami, M., Madmoni, H., Nobe, Y., Doniger, T., Cohen-Chalamish, S. and Prina, E.

Sunday Paper 3

Leishmania parasites depend on flexible gene expression strategies to survive as they cycle between insect vectors and mammalian hosts. This study demonstrates how stage-specific ribosomal RNA (rRNA) modifications provide this essential translational plasticity. The authors mapped the parasite’s rRNA 2′-O-methylation landscape, identifying key modifications guided by small nucleolar RNAs (snoRNAs). The concept of “specialized ribosomes” poses that ribosomes are not merely passive molecular factories but structurally diverse machines that dynamically regulate gene expression.

Using cytosine base-editing to disrupt the snoRNA responsible for the Am479 modification, researchers demonstrated its essential nature. To resolve how this RNA modification impacts translation, the authors integrated cryo-EM structural biology with robust translatomics methods. They utilized polysome profiling—separating translating polysomes on density gradients to gauge overall translation activity to reveal translational dynamics and transcript-specific regulation. Cryo-EM revealed that the snoRNA functions via a secondary base-pairing interaction, acting as an RNA chaperone to structurally alter helix 68 of the large ribosomal subunit. Polysome profiling and  tRNA-seq showed that this structural change alters the release kinetics of specific tRNAs, thereby selectively re-wiring the translation of a specific subset of mRNAs rather than broadly inhibiting protein synthesis. This provides a profound mechanistic demonstration of specialized ribosomes, revealing how snoRNA-guided structural shifts actively direct the stage-specific translatome in parasites.

Learn more about EIRNABio’s polysome profiling and tRNA-seq services here.