Translatomics for stem cell, cell signalling and antimicrobial resistance
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,
- Xiao, Y. et al. demonstrate that DDX21 maintains hematopoietic stem cell homeostasis, using polysome profiling to show that DDX21 loss disrupts ribosome biogenesis and global translation.
- Li, Y. et al. show that N4BP1 is a negative regulator of IL-17 signalling, using polysome profiling to prove it selectively suppresses the translational efficiency of Act1 mRNA.
- Cueny, R.R. et al. discover that E. coli overcomes G-quadruplex-stabilizing compounds by reprogramming its translation machinery.
RNA helicase DDX21 sustains hematopoietic stem cell homeostasis by preventing nucleolar stress
Cell Investigation, 2026.
Xiao, Y., Pan, J., Fan, J., Wang, W., Chen, S., Yan, Q., Luo, D., Zhao, X., Li, Z. and Hou, Y.
Hematopoietic stem cells (HSCs) rely on stringent regulatory machinery to maintain cell quiescence, self-renewal and prevent stem cell exhaustion. The nucleolus acts as the central hub for ribosome biogenesis, a process tightly coupled to protein synthesis and cellular metabolic state. The RNA helicase DDX21 plays critical roles in ribosomal RNA (rRNA) transcription and processing, but its specific function in primary HSC homeostasis has remained poorly defined.
This study demonstrates that DDX21 expression is essential for maintaining functional adult hematopoietic stem cells pools. Loss or dysregulation of DDX21 triggers severe nucleolar stress, disrupting nucleolar architecture and leading to aberrant ribosome biogenesis. Polysome profiling revealed a reduction in 40S and 60S ribosomal subunits as well as 80S monosomes in Ddx21-knockout murine HSCs. This quantitative loss of functional ribosomes severely impairs global protein translation and triggers p53-dependent activation of apoptosis, driving premature HSC exhaustion. Restoring DDX21 rescues rRNA processing, attenuates nucleolar stress, and preserves long-term HSC reconstituting capacity in vivo.
These findings identify DDX21 as a vital safeguard of adult stem cell proteostasis. By leveraging polysome profiling to reveal impaired ribosome biogenesis, the study establishes a direct link between nucleolar helicase activity, active ribosome supply, and translational regulation in regulating stem cell fate.
Learn more about EIRNABio’s polysome profiling services here.
N4BP1 acts as a potent negative regulator of IL-17 signalling by blocking the translation of Act1 mRNA
Inflammation Research, 2026.
Li, Y., Xu, Z., Zhang, X., Zhang, Z., Ji, C., Guo, X., Zhang, J., Feng, P., Mao, R., Liu, Z., Lu, Y, and Fan, Y.
Interleukin-17 (IL-17) is a key pro-inflammatory cytokine driving pathology in autoimmune diseases such as psoriasis and asthma. Binding of IL-17 to its receptor recruits nuclear factor-κB activator 1 (Act1), an essential adaptor protein that triggers downstream transcription of inflammatory genes. While transcriptional regulation of IL-17 signalling is well studied, the post-transcriptional and translational mechanisms regulating Act1 protein abundance remain less understood.
This study identifies the endoribonuclease N4BP1 as a potent negative regulator of IL-17 signalling via suppression of Act1. Previous work established that N4BP1 deficiency amplifies IL-17-induced expression of inflammatory mediators (including CXCL1, CCL20, and MMP9) and hyperactivates p38 MAPK signalling in vitro and in vivo. N4BP1 typically promotes mRNA decay, therefore, the authors investigated whether N4BP1 targets the Act1 transcript. Results showed that N4BP1 deficiency did not alter Act1 mRNA synthesis, stability, or decay rates; instead, loss of N4BP1 selectively elevated Act1 protein levels. To further understand this mechanism, the authors performed polysome profiling, which revealed that N4BP1 directly suppresses the translational efficiency of Act1 mRNA. In N4BP1-deficient and knockout cells, Act1 transcripts shifted significantly into translationally active polysome fractions while total mRNA abundance remained unchanged.
These results highlight polysome profiling as the crucial assay that pinpointed translational control as the precise mechanism by which N4BP1 acts as a molecular brake on IL-17 signalling. Polysome profiling allowed the authors to decouple translational efficiency from transcription and mRNA decay, establishing N4BP1-mediated translational repression of Act1 as a major target in IL-17-driven inflammatory and autoimmune diseases.
Learn more about EIRNABio’s polysome profiling services here.
Altering translation allows E. coli to overcome G-quadruplex stabilizers
Nucleic Acids Research, 2025.
Cueny, R.R., Voter, A.F., McKenzie, A.M., Morgenstern, M., Myers, K.S., Place, M.M., Peters, J.M., Coon, J.J. and Keck, J.L.
G-quadruplexes (G4s) are secondary nucleic acid structures that can inhibit replication, transcription, and translation. Small molecules that stabilize G4 structures serve as potential antimicrobial agents by inducing DNA damage and inhibiting transcription. However, bacteria rapidly evolve resistance to these targeted therapies. This study aimed to understand the precise molecular mechanisms that Escherichia coli uses to overcome G4-stabilizing drugs which is critical for advancing G4-targeted drug discovery.
Results revealed that E. coli bypasses the inhibitory effects of G4-stabilizer molecules by strategically reprogramming its translation machinery. Using genetic screens paired with multi-omics approaches, this study discovered that adaptive mutations in ribosomal proteins and translation factors modulate global translation rates. To directly evaluate these translational shifts under G4-stabilizing stress, polysome profiling was used. Polysome profiling demonstrated that G4-stabilizer treatment triggers profound reorganizations in polysome assembly, shifting mRNA distribution from polysome to monosome fractions. Rather than suffering complete translational failure, resistant E. coli strains show decrease in translation initiation and elongation, allowing cells to maintain some protein synthesis and cell growth despite G4-induced stress.
Ultimately, these findings reveal that E. coli survives G4-stabilizing drugs by intentionally slowing its translation rate. By downregulating ribosome assembly and reducing elongation factors, the bacteria effectively mitigate G4-induced stress. This translational adaptability provides critical insights for developing more effective, resistance-proof G4-targeted antimicrobial therapies.
Learn more about EIRNABio’s polysome profiling services here.