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

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

Cell & Developmental Biology

Research output: Contribution to journal › Article › peer-review

12 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 language	English (US)
Article number	112411
Journal	Cell reports
Volume	42
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2023.112411
State	Published - May 30 2023

Funding

We thank Amy Pandya-Jones and members of the Black Laboratory for helpful discussion regarding the eCLIP-seq study; we thank all members of the Christofk Laboratory for general project discussions. A.C.C. was supported by the UCLA Vascular Biology Training Grant ( 5T32HL069766 ). H.R.C. was supported by R01CA215185 and R01AR070245 .

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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10.1016/j.celrep.2023.112411

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title = "ZFP36-mediated mRNA decay regulates metabolism",

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",

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

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year = "2023",

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day = "30",

doi = "10.1016/j.celrep.2023.112411",

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AU - Cicchetto, Andrew C.

AU - Jacobson, Elsie C.

AU - Sunshine, Hannah

AU - Wilde, Blake R.

AU - Krall, Abigail S.

AU - Jarrett, Kelsey E.

AU - Sedgeman, Leslie

AU - Turner, Martin

AU - Plath, Kathrin

AU - Iruela-Arispe, M. Luisa

AU - de Aguiar Vallim, Thomas Q.

AU - Christofk, Heather R.

PY - 2023/5/30

Y1 - 2023/5/30

N2 - 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.

AB - 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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ZFP36-mediated mRNA decay regulates metabolism

Abstract

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Keywords

ASJC Scopus subject areas

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