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Cpeb1b-mediated cytoplasmic polyadenylation of shha mRNA modulates zebrafish definitive hematopoiesis

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Significance HSPCs have the capacities of both self-renewal and multilineage differentiation and hold great importance for lifelong blood supply. The developmental signals ensure the production of HSPCs through endothelial-to-hematopoietic transition… Click to show full abstract

Significance HSPCs have the capacities of both self-renewal and multilineage differentiation and hold great importance for lifelong blood supply. The developmental signals ensure the production of HSPCs through endothelial-to-hematopoietic transition during vertebrate embryogenesis. However, how these signals are accurately regulated to execute cell fate transition remains elusive. In this study, we explore the role of Cpeb1b in HSPC production and uncover its function via cytoplasmic polyadenylation of shha mRNA in this process. We show that notochord-expressed Cpeb1b is required for HSPC development by regulating Hedgehog signaling. Cpeb1b interacts with shha mRNA in the liquid-like condensates and promotes its cytoplasmic polyadenylation. Cytoplasmic polyadenylation of shha mRNA enhances its own translation efficiency and therefore increases the Shha protein level, which facilitates Hedgehog signaling activation.

Keywords: cpeb1b; shha mrna; polyadenylation shha; cytoplasmic polyadenylation

Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2023

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