ZFP36-mediated mRNA decay regulates metabolism
Summary: 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 m...
Main Authors: | , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2023-05-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723004229 |
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author | 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 |
author_facet | 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 |
author_sort | Andrew C. Cicchetto |
collection | DOAJ |
description | Summary: 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. |
first_indexed | 2024-04-09T16:44:47Z |
format | Article |
id | doaj.art-73e0963b38cb4fecacd111d48dec773f |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-04-09T16:44:47Z |
publishDate | 2023-05-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
spelling | doaj.art-73e0963b38cb4fecacd111d48dec773f2023-04-23T06:06:04ZengElsevierCell Reports2211-12472023-05-01425112411ZFP36-mediated mRNA decay regulates metabolismAndrew C. Cicchetto0Elsie C. Jacobson1Hannah Sunshine2Blake R. Wilde3Abigail S. Krall4Kelsey E. Jarrett5Leslie Sedgeman6Martin Turner7Kathrin Plath8M. Luisa Iruela-Arispe9Thomas Q. de Aguiar Vallim10Heather R. Christofk11Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USADepartment of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USADepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USADepartment of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USADepartment of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USADepartment of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USADepartment of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USAImmunology Programme, The Babraham Institute, Cambridge, UKDepartment 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, USADepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USADepartment 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, USADepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723004229CP: MetabolismCP: Molecular biology |
spellingShingle | 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 ZFP36-mediated mRNA decay regulates metabolism Cell Reports CP: Metabolism CP: Molecular biology |
title | ZFP36-mediated mRNA decay regulates metabolism |
title_full | ZFP36-mediated mRNA decay regulates metabolism |
title_fullStr | ZFP36-mediated mRNA decay regulates metabolism |
title_full_unstemmed | ZFP36-mediated mRNA decay regulates metabolism |
title_short | ZFP36-mediated mRNA decay regulates metabolism |
title_sort | zfp36 mediated mrna decay regulates metabolism |
topic | CP: Metabolism CP: Molecular biology |
url | http://www.sciencedirect.com/science/article/pii/S2211124723004229 |
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