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
(all 7)
PubMed
36745802 Full text @ Proc. Natl. Acad. Sci. USA
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
Marker Marker Type Name
cpeb1bGENEcytoplasmic polyadenylation element binding protein 1b
dll4GENEdelta-like 4 (Drosophila)
efnb2aGENEephrin-B2a
foxaGENEforkhead box A sequence
gapdhGENEglyceraldehyde-3-phosphate dehydrogenase
gata1aGENEGATA binding protein 1a
gfi1aaGENEgrowth factor independent 1A transcription repressor a
gli1GENEGLI family zinc finger 1
hey1GENEhes-related family bHLH transcription factor with YRPW motif 1
hey2GENEhes-related family bHLH transcription factor with YRPW motif 2
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Figures
Figure Gallery (7 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
jh11TgTransgenic Insertion
    s896TgTransgenic Insertion
      y1TgTransgenic Insertion
        zf128TgTransgenic Insertion
          zf169TgTransgenic Insertion
            zko2197A
              		Small Deletion
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              Target Reagent Reagent Type
              cpeb1bCRISPR1-cpeb1bCRISPR
              cpeb1bMO1-cpeb1bMRPHLNO
              pabpc1bMO1-pabpc1bMRPHLNO
              shhaMO1-shhaMRPHLNO
              1 - 4 of 4
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              Fish
              Antibodies
              Orthology
              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              GFPEFGGFP
              mCherryEFGmCherry
              1 - 3 of 3
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              Mapping
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              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.