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Publication : ZFP36-mediated mRNA decay regulates metabolism.

First Author  Cicchetto AC Year  2023
Journal  Cell Rep Volume  42
Issue  5 Pages  112411
PubMed ID  37086408 Mgi Jnum  J:341038
Mgi Id  MGI:7491472 Doi  10.1016/j.celrep.2023.112411
Citation  Cicchetto AC, et al. (2023) ZFP36-mediated mRNA decay regulates metabolism. Cell Rep 42(5):112411
abstractText  Cellular metabolism is tightly regulated by growth factor signaling, which promotes metabolic rewiring to support growth and proliferation. While growth factor-induced transcriptional and post-translational modes of metabolic regulation have been well defined, whether post-transcriptional mechanisms impacting mRNA stability regulate this process is less clear. Here, we present the ZFP36/L1/L2 family of RNA-binding proteins and mRNA decay factors as key drivers of metabolic regulation downstream of acute growth factor signaling. We quantitatively catalog metabolic enzyme and nutrient transporter mRNAs directly bound by ZFP36 following growth factor stimulation-many of which encode rate-limiting steps in metabolic pathways. Further, we show that ZFP36 directly promotes the mRNA decay of Enolase 2 (Eno2), altering Eno2 protein expression and enzymatic activity, and provide evidence of a ZFP36/Eno2 axis during VEGF-stimulated developmental retinal angiogenesis. Thus, ZFP36-mediated mRNA decay serves as an important mode of metabolic regulation downstream of growth factor signaling within dynamic cell and tissue states.
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