PUBLICATION
Cpeb1b-mediated cytoplasmic polyadenylation of shha mRNA modulates zebrafish definitive hematopoiesis
- Authors
- Heng, J., Shi, B., Zhou, J.Y., Zhang, Y., Ma, D., Yang, Y.G., Liu, F.
- ID
- ZDB-PUB-230207-25
- Date
- 2023
- Source
- Proceedings of the National Academy of Sciences of the United States of America 120: e2212212120e2212212120 (Journal)
- Registered Authors
- Liu, Feng, Ma, Dongyuan
- Keywords
- Cpeb1b, Hedgehog signaling, cytoplasmic polyadenylation, hematopoietic stem and progenitor cell, translational control
- MeSH Terms
-
- Animals
- Hedgehog Proteins/metabolism
- Hematopoiesis/genetics
- Polyadenylation*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Zebrafish*/metabolism
- PubMed
- 36745802 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Heng, J., Shi, B., Zhou, J.Y., Zhang, Y., Ma, D., Yang, Y.G., Liu, F. (2023) Cpeb1b-mediated cytoplasmic polyadenylation of shha mRNA modulates zebrafish definitive hematopoiesis. Proceedings of the National Academy of Sciences of the United States of America. 120:e2212212120e2212212120.
Abstract
During vertebrate embryogenesis, hematopoietic stem and progenitor cell (HSPC) production through endothelial-to-hematopoietic transition requires suitable developmental signals, but how these signals are accurately regulated remains incompletely understood. Cytoplasmic polyadenylation, which is one of the posttranscriptional regulations, plays a crucial role in RNA metabolism. Here, we report that Cpeb1b-mediated cytoplasmic polyadenylation is important for HSPC specification by translational control of Hedgehog (Hh) signaling during zebrafish early development. Cpeb1b is highly expressed in notochord and its deficiency results in defective HSPC production. Mechanistically, Cpeb1b regulates hemogenic endothelium specification by the Hedgehog-Vegf-Notch axis. We demonstrate that the cytoplasmic polyadenylation element motif-dependent interaction between Cpeb1b and shha messenger RNA (mRNA) in the liquid-like condensates, which are induced by Pabpc1b phase separation, is required for cytoplasmic polyadenylation of shha mRNA. Intriguingly, the cytoplasmic polyadenylation regulates translation but not stability of shha mRNA, which further enhances the Shha protein level and Hh signal transduction. Taken together, our findings uncover the role of Cpeb1b-mediated cytoplasmic polyadenylation in HSPC development and provide insights into how posttranscriptional regulation can direct developmental signals with high fidelity to translate them into cell fate transition.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping