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

doi:10.1016/j.celrep.2023.112411

ZFP36-mediated mRNA decay regulates metabolism

Cell Rep. 2023 May 30;42(5):112411. doi: 10.1016/j.celrep.2023.112411. Epub 2023 Apr 21.

Affiliations

¹ Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
² Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
³ Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USA.
⁴ Immunology Programme, The Babraham Institute, Cambridge, UK.
⁵ Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
⁶ Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USA; Molecular Biology Institute, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA.
⁷ Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA. Electronic address: hchristofk@mednet.ucla.edu.

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.

Keywords: CP: Metabolism; CP: Molecular biology; RNA-binding proteins; growth factor signaling; mRNA stability; metabolism.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Intercellular Signaling Peptides and Proteins / metabolism
RNA Stability / genetics
RNA-Binding Proteins* / genetics
RNA-Binding Proteins* / metabolism
Signal Transduction*
Tristetraprolin / genetics
Tristetraprolin / metabolism

Substances

RNA-Binding Proteins
Intercellular Signaling Peptides and Proteins
Tristetraprolin

ZFP36-mediated mRNA decay regulates metabolism

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding