PUBLICATION
Prkra dimer senses double-stranded RNAs to dictate global translation efficiency
- Authors
- Lu, T., Ma, P., Fang, H., Chen, A., Xu, J., Kuang, X., Wang, M., Su, L., Wang, S., Zhang, Y., Wang, J., Yang, B., Shi, D.L., Zhou, Y., Gong, Q., Liu, X., Mao, B., Shao, M.
- ID
- ZDB-PUB-250427-3
- Date
- 2025
- Source
- Molecular Cell : (Journal)
- Registered Authors
- Shao, Ming, Shi, De-Li
- Keywords
- PACT/RAX, Prkra, double-stranded RNA, dsRNA sensor, early embryos, embryonic stem cells, translation initiation
- MeSH Terms
-
- Animals
- Eukaryotic Initiation Factor-2/genetics
- Eukaryotic Initiation Factor-2/metabolism
- Humans
- Mice
- Mouse Embryonic Stem Cells/enzymology
- Mouse Embryonic Stem Cells/metabolism
- Mouse Embryonic Stem Cells/virology
- Protein Biosynthesis*
- Protein Multimerization
- RNA, Double-Stranded*/genetics
- RNA, Double-Stranded*/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/chemistry
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- eIF-2 Kinase*/genetics
- eIF-2 Kinase*/metabolism
- PubMed
- 40280134 Full text @ Mol. Cell
Citation
Lu, T., Ma, P., Fang, H., Chen, A., Xu, J., Kuang, X., Wang, M., Su, L., Wang, S., Zhang, Y., Wang, J., Yang, B., Shi, D.L., Zhou, Y., Gong, Q., Liu, X., Mao, B., Shao, M. (2025) Prkra dimer senses double-stranded RNAs to dictate global translation efficiency. Molecular Cell. :.
Abstract
Double-stranded RNAs (dsRNAs), known as conserved pathogen-associated molecular patterns, activate the integrated stress response via interferon-induced protein kinase R (PKR), leading to global translation inhibition. However, the interferon system is inactive in pluripotent cells, leaving the mechanisms of dsRNA sensing and translational control unclear. In this study, we utilized early zebrafish embryos as a model of pluripotent cells and discovered a PKR-independent blockage of translation initiation by dsRNA stimulation. Prkra dimer was identified as the genuine dsRNA sensor. Upon dsRNA binding, the dimerized dsRNA-binding domain 3 of Prkra becomes activated to sequester the eIF2 complexes from the translation machinery, inhibiting global protein synthesis. This distinctive embryonic stress response restricts RNA virus replication in zebrafish embryos, is conserved in mouse embryonic stem cells, and compensates PKR function in differentiated cells. Therefore, the Prkra-mediated dsRNA sensing and translation control may serve as a common strategy for cells to adapt to environmental stresses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping