MicroRNA profiling reveals miR‐145‐5p inhibits goat myoblast differentiation by targeting the coding domain sequence of USP13

Zhang, Zhen; Deng, Kaiping; Kang, Ziqi; Wang, Feng; Fan, Yixuan

doi:10.1096/fj.202200246r

Cited by 10 publications

(7 citation statements)

References 57 publications

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“…1B ). Consistent with previous literature [ 7 , 8 , 25 , 26 ], the knockdown of SENP2, USP7, USP10 and USP13, had a detrimental effect on muscle cell fusion (Fig. 1B, C ).…”

Section: Resultssupporting

confidence: 92%

USP18 is an essential regulator of muscle cell differentiation and maturation

et al. 2023

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The ubiquitin proteasomal system is a critical regulator of muscle physiology, and impaired UPS is key in many muscle pathologies. Yet, little is known about the function of deubiquitinating enzymes (DUBs) in the muscle cell context. We performed a genetic screen to identify DUBs as potential regulators of muscle cell differentiation. Surprisingly, we observed that the depletion of ubiquitin-specific protease 18 (USP18) affected the differentiation of muscle cells. USP18 depletion first stimulated differentiation initiation. Later, during differentiation, the absence of USP18 expression abrogated myotube maintenance. USP18 enzymatic function typically attenuates the immune response by removing interferon-stimulated gene 15 (ISG15) from protein substrates. However, in muscle cells, we found that USP18, predominantly nuclear, regulates differentiation independent of ISG15 and the ISG response. Exploring the pattern of RNA expression profiles and protein networks whose levels depend on USP18 expression, we found that differentiation initiation was concomitant with reduced expression of the cell-cycle gene network and altered expression of myogenic transcription (co) factors. We show that USP18 depletion altered the calcium channel gene network, resulting in reduced calcium flux in myotubes. Additionally, we show that reduced expression of sarcomeric proteins in the USP18 proteome was consistent with reduced contractile force in an engineered muscle model. Our results revealed nuclear USP18 as a critical regulator of differentiation initiation and maintenance, independent of ISG15 and its role in the ISG response.

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“…1B ). Consistent with previous literature [ 7 , 8 , 25 , 26 ], the knockdown of SENP2, USP7, USP10 and USP13, had a detrimental effect on muscle cell fusion (Fig. 1B, C ).…”

Section: Resultssupporting

confidence: 92%

USP18 is an essential regulator of muscle cell differentiation and maturation

et al. 2023

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“…However, cell count was not dramatically affected by DUBs siRNA transfection, with the exception of USP20 (Fig. 1B) Consistent with previous literature 7,8,25,26 , the knockdown of DUBs, such as SENP2, USP7, USP10 and USP13, had a detrimental effect on muscle cell fusion (Fig. 1C).…”

Section: Resultssupporting

confidence: 91%

USP18 is an essential regulator of muscle cell differentiation and maturation

Olie

Pinto-Fernández

Damianou

et al. 2022

Preprint

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Muscle degeneration, a key feature in a wide range of human pathologies, is typified by impaired proteastasis, in which the ubiquitin proteasomal system in particular plays an important role. Yet, little is known about the function of deubiquitinating enzymes (DUBs) in muscle cell biology. We performed a genetic screen to identify DUBs regulators of muscle cell differentiation. Surprisingly, we observed that USP18-depletion induced differentiation and reduced proliferation of muscle cells. USP18 enzymatic function typically attenuates the immune response by removing ISG15, but in muscle cells, we found that USP18 regulates differentiation independent of ISG15 and the IFN-1 pathway. USP18 accumulation in muscle cell nuclei was concomitant with reduced expression of the cell-cycle gene network and altered transcription-regulated gene networks, including myogenic transcription factors. Additionally, USP18-depletion altered calcium channel gene networks, which was in line with reduced calcium flux in myotubes. Reduced sarcomeric genes were linked to reduced contractile force in an engineered muscle model. Our results revealed nuclear USP18 as a critical regulator of differentiation initiation and differentiation maintenance, independent of the IFN-1 pathway.

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“…Potential target sites of circCSDE1 included miR-10382, miR-22-5p, miR-21-3p, miR-145-5p and miR-885-5p. Only miR-145-5p was reported to inhibit myoblast differentiation [ 21 ]. However, the expression of miR-145-5p did not differ among three treatment groups.…”

Section: Discussionmentioning

confidence: 99%

CircCSDE1 Regulates Proliferation and Differentiation of C2C12 Myoblasts by Sponging miR-21-3p

Sun

Cui

et al. 2022

IJMS

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The growth and development of skeletal muscle is regulated by many factors, and recent studies have shown that circular RNAs (circRNAs) can participate in this process. The model of porcine skeletal muscle injury was constructed to search for circRNAs that can regulate the growth and development of skeletal muscle in pigs. Using whole-transcriptome sequencing and bioinformatics analysis, a novel circRNA (circCSDE1) was screened out, which is highly expressed in skeletal muscle. Functional studies in C2C12 cells demonstrated that circCSDE1 could promote proliferation and inhibit myoblast differentiation, while opposing changes were observed by circCSDE1 knockdown. A dual-luciferase reporter assay revealed that circCSDE1 directly targeted miR-21-3p to regulate the expression of the downstream target gene (Cyclin-dependent kinase 16, CDK16). Moreover, miR-21-3p could inhibit proliferation and promote myoblast differentiation in C2C12 cells, opposite with the effects of circCSDE1. Additionally, the rescue experiments offered further evidence that circCSDE1 and its target, miR-21-3p, work together to regulate myoblast proliferation and differentiation. This study provides a theoretical basis for further understanding the regulatory mechanisms of circRNAs.

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MicroRNA profiling reveals miR‐145‐5p inhibits goat myoblast differentiation by targeting the coding domain sequence of USP13

Cited by 10 publications

References 57 publications

USP18 is an essential regulator of muscle cell differentiation and maturation

USP18 is an essential regulator of muscle cell differentiation and maturation

USP18 is an essential regulator of muscle cell differentiation and maturation

CircCSDE1 Regulates Proliferation and Differentiation of C2C12 Myoblasts by Sponging miR-21-3p

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