Translatomics for mito-ribosomes, EIF3D, and selenoprotein
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,
- Schöndorf, T. et al. through ribosome profiling and cryo-EM of mito-ribosomes show that inner mitochondrial membrane insertion acts as a kinetic checkpoint, coordinating protein folding, topology establishment, and translation speed.
- Okubo, C. et al. through CRISPRi screens and polysome profiling show that translational regulation via EIF3D acts as a key link between signalling pathways and pluripotency networks
- Zhang, X. et al. find a novel mechanism linking phase separation, translational control, and cancer progression.
Membrane insertion of mitochondrial-encoded proteins regulates ribosome decoding speed
Nature Structure and Molecular Biology, 2026
Schöndorf, T., Petrychenko, V., Kotan, I., Dahal, D., Napieraj, N., Cruz-Zaragoza, L.D., Wang, C., Urbach, O., Gall, T., Dennerlein, S., Kramer, G., Fischer, N. & Rehling, P.
The paper investigates how the co-translational insertion of mitochondrial-encoded OXPHOS subunits into the inner mitochondrial membrane (IMM) is coupled to the dynamics of the mitochondrial ribosome vestibule at the exit tunnel. Using MNase-based ribosome profiling and cryo-EM snapshots of paused mito-ribosomes, the authors show that translation is not uniform but instead dynamically modulated during membrane protein synthesis. A key finding is that ribosome decoding speed slows at specific regions, particularly near transmembrane helices (TMHs) and topological regions. The authors suggest that some pauses coincide with topology-establishing events, including hairpin-loop formation before membrane insertion, while the cryo-EM data directly show folding of the COX1 nascent chain into a small α-helix within the mitoribosomal vestibule.
Thus, the physical process of membrane insertion feeds back to regulate translation speed. The study also identifies pausing for COX1 at ~0-10 codons and at ~25-35 codons, the latter coinciding with entry and folding of the N-terminal COX1 α-helix within the vestibule. Structural data reveal intermediates of ribosome–insertase (OXA1L) complexes, showing how mitochondrial ribosomes are spatially and functionally coupled to the membrane insertion machinery. Overall, the authors propose that membrane insertion acts as a kinetic checkpoint, coordinating protein folding, topology establishment, and translation speed. This ensures accurate biogenesis of mitochondrial membrane proteins and highlights a direct mechanistic link between translation and membrane integration.
Learn more about EIRNABio’s ribosome profiling services here.
EIF3D safeguards the homeostasis of key signalling pathways in human primed pluripotency
Science Advances, 2025
Okubo, C., Nakamura, M., Sato, M., Shichino, Y., Mito, M., Takashima, Y., Iwasaki, S. and Takahashi, K.
The study identifies EIF3D, a subunit of the eukaryotic translation initiation factor 3 complex, as a critical regulator of human primed pluripotent stem cell (PSC) homeostasis. Using CRISPRi-mediated knockdown (KD), the authors show that loss of EIF3D rapidly impairs PSC translation, proliferation, self-renewal, and differentiation into all three germ layers. The early phenotype is unlikely to be simply a consequence of cellular stress, because reduced translation, loss of pluripotency, and p53-pathway changes were evident by day 3, whereas increased eIF2α phosphorylation was not detected until day 5. EIF3D depletion leads to strong activation of the p53 pathway including increased p53 protein expression, resulting in cell cycle arrest and reduced proliferation, highlighting its role in suppressing p53 activity via translational control of its regulators.
Polysome profiling showed an accumulation of 80S ribosomes following EIF3D depletion, consistent with impaired translation initiation, while puromycin incorporation showed that de novo protein synthesis fell to approximately 45% of control levels. Ribosome profiling then identified transcript-specific changes in translational efficiency, including reduced translation of genes involved in several pluripotency-associated signalling pathways and of multiple p53 regulators. Thus, EIF3D depletion causes both a substantial reduction in global translation and selective translational dysregulation. Additionally, EIF3D influences phosphorylation and protein expression across multiple signalling networks, including mTOR-related pathways, indicating a broad role in maintaining signalling equilibrium. Although EIF3D interacts with EIF4G2, EIF3D knockdown produced a distinct and more rapidly developing phenotype than EIF4G2 knockdown, supporting nonredundant functions in primed PSCs. Overall, the study demonstrates that translational regulation via EIF3D acts as a key link between signalling pathways and pluripotency networks, ensuring proper cell proliferation and developmental potential in primed PSCs.
Learn more about EIRNABio’s ribosome profiling and polysome profiling services here.
Phase separation of TRNAU1AP protein sustains selenoprotein translation and promotes glioblastoma tumorigenesis
Neuro-Oncology, 2026
Zhang, X., Li, L., Li, L., Yu, S., Ouyang, T., Han, X., Joh, R.I., Chen, Y., Wang, H. and Huang, S.
The study identifies TRNAU1AP as a key regulator of selenoprotein synthesis and glioblastoma (GBM) tumorigenesis. TRNAU1AP is highly expressed in GBM and correlates with poor patient prognosis and stemness features. Functionally, it is essential for glioblastoma stem cell proliferation, self-renewal, and tumor growth. Mechanistically, TRNAU1AP undergoes liquid–liquid phase separation (LLPS) via its conserved tyrosine-rich domain, forming condensates that spatially organize the selenoprotein translation machinery. Within these condensates, TRNAU1AP interacts with EEFSEC and enhances its binding to Sec-tRNAsec, thereby selectively promoting the translation of selenoproteins. Polysome profiling in this study demonstrates that TRNAU1AP selectively enhances the translation efficiency of selenoprotein mRNAs rather than globally affecting protein synthesis. By analyzing ribosome loading, the authors show that depletion of TRNAU1AP shifts key selenoprotein transcripts from heavy polysomes to lighter fractions, indicating reduced active translation. This provides direct evidence that TRNAU1AP promotes efficient ribosome engagement on specific mRNAs, particularly those requiring specialized machinery like selenocysteine incorporation. Upstream, the m6A reader IGF2BP3 drives TRNAU1AP overexpression by stabilizing its mRNA in an m6A-dependent manner. The IGF2BP3–TRNAU1AP axis enhances selenoprotein expression, stemness, and tumorigenicity in GBM models. Overall, the study reveals a novel mechanism linking phase separation, translational control, and cancer progression, positioning TRNAU1AP as a potential therapeutic target in glioblastoma.
Learn more about EIRNABio’s polysome profiling services here.