A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size

Summary: Skeletal muscle size is controlled by the balance between protein synthesis and protein degradation. Given the essential role of skeletal muscle in maintaining a high quality of life, understanding the mechanisms that modulate this balance are of critical importance. Previously, we demonstr...

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Main Authors: Nathaniel D. Steinert, Kent W. Jorgenson, Kuan-Hung Lin, Jake B. Hermanson, Jake L. Lemens, Troy A. Hornberger
Format: Article
Language:English
Published: Elsevier 2023-04-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S258900422300603X
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author Nathaniel D. Steinert
Kent W. Jorgenson
Kuan-Hung Lin
Jake B. Hermanson
Jake L. Lemens
Troy A. Hornberger
author_facet Nathaniel D. Steinert
Kent W. Jorgenson
Kuan-Hung Lin
Jake B. Hermanson
Jake L. Lemens
Troy A. Hornberger
author_sort Nathaniel D. Steinert
collection DOAJ
description Summary: Skeletal muscle size is controlled by the balance between protein synthesis and protein degradation. Given the essential role of skeletal muscle in maintaining a high quality of life, understanding the mechanisms that modulate this balance are of critical importance. Previously, we demonstrated that muscle-specific knockout of TRIM28 reduces muscle size and function and in the current study, we discovered that this effect is associated with an increase in protein degradation and a dramatic reduction in the expression of Mettl21c. Importantly, we also determined that overexpression of Mettl21c is sufficient to induce hypertrophy in both control and TRIM28 knockout muscles. Moreover, we developed a simple pulse-chase biorthogonal non-canonical amino acid tagging technique that enabled us to visualize the in vivo rate of protein degradation, and with this technique were able to conclude that the hypertrophic effect of Mettl21c is due, at least in part, to an inhibition of protein degradation.
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spelling doaj.art-f350e5a34bf94357b778af9c6864303c2023-04-12T04:12:09ZengElsevieriScience2589-00422023-04-01264106526A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle sizeNathaniel D. Steinert0Kent W. Jorgenson1Kuan-Hung Lin2Jake B. Hermanson3Jake L. Lemens4Troy A. Hornberger5Department of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA; School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USADepartment of Molecular and Cellular Pharmacology, University of Wisconsin - Madison, Madison, WI, USA; School of Medicine and Public Health, University of Wisconsin - Madison, Madison, WI, USADepartment of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA; School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USADepartment of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA; School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USADepartment of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA; School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USADepartment of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA; School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USA; Corresponding authorSummary: Skeletal muscle size is controlled by the balance between protein synthesis and protein degradation. Given the essential role of skeletal muscle in maintaining a high quality of life, understanding the mechanisms that modulate this balance are of critical importance. Previously, we demonstrated that muscle-specific knockout of TRIM28 reduces muscle size and function and in the current study, we discovered that this effect is associated with an increase in protein degradation and a dramatic reduction in the expression of Mettl21c. Importantly, we also determined that overexpression of Mettl21c is sufficient to induce hypertrophy in both control and TRIM28 knockout muscles. Moreover, we developed a simple pulse-chase biorthogonal non-canonical amino acid tagging technique that enabled us to visualize the in vivo rate of protein degradation, and with this technique were able to conclude that the hypertrophic effect of Mettl21c is due, at least in part, to an inhibition of protein degradation.http://www.sciencedirect.com/science/article/pii/S258900422300603XBiochemistryCell biologyDevelopmental biology
spellingShingle Nathaniel D. Steinert
Kent W. Jorgenson
Kuan-Hung Lin
Jake B. Hermanson
Jake L. Lemens
Troy A. Hornberger
A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size
iScience
Biochemistry
Cell biology
Developmental biology
title A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size
title_full A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size
title_fullStr A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size
title_full_unstemmed A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size
title_short A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size
title_sort novel method for visualizing in vivo rates of protein degradation provides insight into how trim28 regulates muscle size
topic Biochemistry
Cell biology
Developmental biology
url http://www.sciencedirect.com/science/article/pii/S258900422300603X
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