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ZFP36-mediated mRNA decay regulates metabolism.

Authors :: Cicchetto AC
Jacobson EC
Sunshine H
Wilde BR
Krall AS
Jarrett KE
Sedgeman L
Turner M
Plath K
Iruela-Arispe ML
de Aguiar Vallim TQ
Christofk HR
Source :: Cell reports [Cell Rep] 2023 May 30; Vol. 42 (5), pp. 112411. Date of Electronic Publication: 2023 Apr 21.
Publication Year :: 2023
Abstract: 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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)