ZFP36-mediated mRNA decay regulates metabolism

Andrew C. Cicchetto, Elsie C. Jacobson, Hannah Sunshine, Blake R. Wilde, Abigail S. Krall, Kelsey E. Jarrett, Leslie Sedgeman, Martin Turner, Kathrin Plath, M. Luisa Iruela-Arispe, Thomas Q. de Aguiar Vallim, Heather R. Christofk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Article number112411
JournalCell reports
Volume42
Issue number5
DOIs
StatePublished - May 30 2023

Keywords

  • CP: Metabolism
  • CP: Molecular biology
  • RNA-binding proteins
  • growth factor signaling
  • mRNA stability
  • metabolism

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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