scholarly journals The microprotein Minion controls cell fusion and muscle formation

2017 ◽  
Author(s):  
Qiao Zhang ◽  
Ajay Vashisht ◽  
Jason O’Rourke ◽  
Stéphane Y. Corbel ◽  
Rita Moran ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Fusion ◽  
Noncoding Rna ◽  
Muscle Development ◽  
Transmembrane Protein ◽  
Loss Of Function ◽  
Reading Frame ◽  
Muscle Formation ◽  
Small Open Reading Frame ◽  
Cellular Fusion

Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, the functional repertoire of this microproteome remains to be determined1. In skeletal muscle, proper development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process2,3. Here we report the identification of a small ORF encoding an essential skeletal muscle specific microprotein we term Minion (microprotein inducer of fusion). Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally with marked reduction in fused muscle fibers. This fusogenic activity is conserved to the human Minion ortholog, previously annotated as a long noncoding RNA. Loss-of-function studies demonstrate that Minion is the factor providing muscle specific fusogenic function for the transmembrane protein Myomaker4. Remarkably, we demonstrate that co-expression of Minion and Myomaker is sufficient to induce rapid cytoskeletal rearrangement and homogeneous cellular fusion, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component program for the induction of mammalian cell fusion, enabling both research and translational applications. Importantly, these data also significantly expand the known functions of smORF-encoded microproteins, an under-explored source of proteomic diversity.

scholarly journals Weak Electromagnetic Fields Accelerate Fusion of Myoblasts

2021 ◽  
Vol 22 (9) ◽  
pp. 4407
Author(s):  
Dana Adler ◽  
Zehavit Shapira ◽  
Shimon Weiss ◽  
Asher Shainberg ◽  
Abram Katz
Keyword(s):  
Skeletal Muscle ◽  
Cell Membrane ◽  
Cell Fusion ◽  
Electromagnetic Fields ◽  
Muscle Development ◽  
K Channel ◽  
Gambogic Acid ◽  
Cell Replication ◽  
Myotube Formation ◽  
Primary Myoblast

Weak electromagnetic fields (WEF) alter Ca2+ handling in skeletal muscle myotubes. Owing to the involvement of Ca2+ in muscle development, we investigated whether WEF affects fusion of myoblasts in culture. Rat primary myoblast cultures were exposed to WEF (1.75 µT, 16 Hz) for up to six days. Under control conditions, cell fusion and creatine kinase (CK) activity increased in parallel and peaked at 4–6 days. WEF enhanced the extent of fusion after one and two days (by ~40%) vs. control, but not thereafter. Exposure to WEF also enhanced CK activity after two days (almost four-fold), but not afterwards. Incorporation of 3H-thymidine into DNA was enhanced by one-day exposure to WEF (~40%), indicating increased cell replication. Using the potentiometric fluorescent dye di-8-ANEPPS, we found that exposure of cells to 150 mM KCl resulted in depolarization of the cell membrane. However, prior exposure of cells to WEF for one day followed by addition of KCl resulted in hyperpolarization of the cell membrane. Acute exposure of cells to WEF also resulted in hyperpolarization of the cell membrane. Twenty-four hour incubation of myoblasts with gambogic acid, an inhibitor of the inward rectifying K+ channel 2.1 (Kir2.1), did not affect cell fusion, WEF-mediated acceleration of fusion or hyperpolarization. These data demonstrate that WEF accelerates fusion of myoblasts, resulting in myotube formation. The WEF effect is associated with hyperpolarization but WEF does not appear to mediate its effects on fusion by activating Kir2.1 channels.

scholarly journals Mechanism and Functions of Identified miRNAs in Poultry Skeletal Muscle Development – A Review

2019 ◽  
Vol 19 (4) ◽  
pp. 887-904
Author(s):  
Asiamah Amponsah Collins ◽  
Kun Zou ◽  
Zhang Li ◽  
Su Ying
Keyword(s):  
Skeletal Muscle ◽  
Candidate Genes ◽  
Skeletal Muscles ◽  
Muscle Development ◽  
Muscle Growth ◽  
Skeletal Muscle Development ◽  
Single Nucleotide ◽  
Complex Processes ◽  
Muscle Formation ◽  
Gene Regulatory

AbstractDevelopment of the skeletal muscle goes through several complex processes regulated by numerous genetic factors. Although much efforts have been made to understand the mechanisms involved in increased muscle yield, little work is done about the miRNAs and candidate genes that are involved in the skeletal muscle development in poultry. Comprehensive research of candidate genes and single nucleotide related to poultry muscle growth is yet to be experimentally unraveled. However, over a few periods, studies in miRNA have disclosed that they actively participate in muscle formation, differentiation, and determination in poultry. Specifically, miR-1, miR-133, and miR-206 influence tissue development, and they are highly expressed in the skeletal muscles. Candidate genes such as CEBPB, MUSTN1, MSTN, IGF1, FOXO3, mTOR, and NFKB1, have also been identified to express in the poultry skeletal muscles development. However, further researches, analysis, and comprehensive studies should be made on the various miRNAs and gene regulatory factors that influence the skeletal muscle development in poultry. The objective of this review is to summarize recent knowledge in miRNAs and their mode of action as well as transcription and candidate genes identified to regulate poultry skeletal muscle development.

scholarly journals Transcriptome analysis reveals the long intergenic noncoding RNAs contributed to skeletal muscle differences between Yorkshire and Tibetan pig

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ziying Huang ◽  
Qianqian Li ◽  
Mengxun Li ◽  
Changchun Li
Keyword(s):  
Skeletal Muscle ◽  
Noncoding Rna ◽  
Muscle Development ◽  
Target Genes ◽  
Muscle Growth ◽  
Skeletal Muscle Development ◽  
Tibetan Pig ◽  
The Difference ◽  
Long Intergenic Noncoding Rna

AbstractThe difference between the skeletal muscle growth rates of Western and domestic breeds is remarkable, but the potential regulatory mechanism involved is still unclear. Numerous studies have pointed out that long intergenic noncoding RNA (lincRNA) plays a key role in skeletal muscle development. This study used published Yorkshire (LW) and Tibetan pig (TP) transcriptome data to explore the possible role of lincRNA in the difference in skeletal muscle development between the two breeds. 138 differentially expressed lincRNAs (DELs) were obtained between the two breeds, and their potential target genes (PTGs) were predicted. The results of GO and KEGG analysis revealed that PTGs are involved in multiple biological processes and pathways related to muscle development. The quantitative trait loci (QTLs) of DELs were predicted, and the results showed that most QTLs are related to muscle development. Finally, we constructed a co-expression network between muscle development related PTGs (MDRPTGs) and their corresponding DELs on the basis of their expression levels. The expression of DELs was significantly correlated with the corresponding MDRPTGs. Also, multiple MDRPTGs are involved in the key regulatory pathway of muscle fiber hypertrophy, which is the IGF-1-AKT-mTOR pathway. In summary, multiple lincRNAs that may cause differences in skeletal muscle development between the two breeds were identified, and their possible regulatory roles were explored. The findings of this study may provide a valuable reference for further research on the role of lincRNA in skeletal muscle development.

scholarly journals The circular RNA circCPE regulates myoblast development by sponging miR-138

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenxiu Ru ◽  
Ao Qi ◽  
Xuemei Shen ◽  
Binglin Yue ◽  
Xiaoyan Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Muscle Regeneration ◽  
Noncoding Rna ◽  
Muscle Development ◽  
Circular Rna ◽  
Inhibitory Effect ◽  
Skeletal Muscle Regeneration ◽  
Bovine Muscle

Abstract Background Skeletal muscle development, a long-term and complex process, is controlled by a set of the myogenic genes. Circular RNAs (circRNAs), a class of noncoding RNA, have been shown to regulate various biological processes. Recent studies indicate circRNAs may be involved in myogenesis, but the role and regulatory mechanism of circRNAs in myogenesis is largely unknown. In the present study, circCPE was firstly found to promote the bovine myoblast proliferation and inhibit cell apoptosis and differentiation by influencing the expression of FOXC1 in a miR138-mediated manner. And in vivo experiments revealed that overexpression of circCPE attenuates skeletal muscle regeneration. Results We identified a novel circular RNA circCPE by analyzing circRNAs sequencing data of bovine muscle tissue. Sequencing verification, RNase R treatment and Actinomycin D treatment confirmed the circular nature of circCPE in bovine muscle. Functional assays showed that overexpression of circCPE could inhibit bovine myoblast apoptosis and differentiation, as well as facilitate cell proliferation. Moreover, in vivo experiments revealed that overexpression of circCPE attenuates skeletal muscle regeneration. In consideration of circRNA action as miRNAs sponge, we found that circCPE harbors miR-138 binding sites and absorbed miR-138. Mechanistically, the rescue experiments showed that the overexpression of circCPE can counteract the inhibitory effect of miR-138 on the cell proliferation and the accelerated effects on the differentiation and apoptosis. Subsequently, we found that circCPE sequester the inhibitory effect of miR-138 on FOXC1 so as to involve in myogenesis. Conclusions Collectively, we constructed a novel circCPE/miR-138/FOXC1 regulatory network in bovine myogenesis, which further provide stronger evidence that circRNA involved in muscle development acting as miRNA sponge.

scholarly journals Myomerger induces fusion of non-fusogenic cells and is required for myoblast fusion

2017 ◽  
Author(s):  
Malgorzata E. Quinn ◽  
Qingnian Goh ◽  
Mitsutoshi Kurosaka ◽  
Dilani G. Gamage ◽  
Michael J. Petrany ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Fusion ◽  
Specific Protein ◽  
Myoblast Fusion ◽  
Mammalian Development ◽  
Normal Muscle ◽  
Muscle Formation ◽  
Biochemical Mechanisms ◽  
Genetic Deletion ◽  
Myoblast Cell

AbstractDespite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined1. This lack of knowledge has severely limited our ability to reconstitute cell fusion, which is necessary to decipher the biochemical mechanisms driving plasma membrane merger. Myomaker (Tmem8c) is a muscle-specific protein required for myoblast fusion2,3. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here, we demonstrate that Gm7325, named myomerger, induces the fusion of myomaker-expressing fibroblasts. Cell mixing experiments reveal that while myomaker renders cells fusion-competent, myomerger induces fusogenicity. Thus, myomaker and myomerger confer fusogenic activity to normally non-fusogenic cells. Myomerger is skeletal muscle-specific and only expressed during developmental and regenerative myogenesis. Disruption of myomerger in myoblast cell lines through Cas9-mutagenesis generated non-fusogenic myocytes. Genetic deletion of myomerger in mice results in a paucity of muscle fibers demonstrating a requirement for myomerger in normal muscle formation. Myomerger deficient myocytes exhibit an ability to differentiate and harbor organized sarcomeres, however remain mono-nucleated. These data identify myomerger as a fundamental myoblast fusion protein and establishes a system that begins to reconstitute mammalian cell fusion.

scholarly journals A screen for Twist-interacting proteins identifies Twinstar as a regulator of muscle development during embryogenesis

2021 ◽  
Author(s):  
Mridula Balakrishnan ◽  
Austin Howard ◽  
Shannon F. Yu ◽  
Katie Sommer ◽  
Scott J. Nowak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Development ◽  
Genetic Interaction ◽  
Interacting Proteins ◽  
Loss Of Function ◽  
Myocyte Enhancer Factor 2 ◽  
Muscle Formation ◽  
Key Events ◽  
Double Interaction ◽  
Enhancer Factor

ABSTRACTMyogenesis in Drosophila relies on the activity of the transcription factor Twist during several key events of mesoderm differentiation. To identify the mechanism(s) by which Twist establishes a unique gene expression profile in specific spatial and temporal locales, we employed a yeast-based double interaction screen to discover new Twist-interacting proteins (TIPs) at the myocyte enhancer factor 2 (mef2) and tinman (tinB) myogenic enhancers. We identified a number of proteins that interacted with Twist at one or both enhancers, and whose interactions with Twist and roles in muscle development were previously unknown. Through genetic interaction studies, we find that Twinstar (Tsr), and its regulators are required for muscle formation. Loss of function and null mutations in tsr and its regulators result in missing and/or misattached muscles. Our data suggest that the yeast double interaction screen is a worthy approach to investigate spatial-temporal mechanisms of transcriptional regulation in muscle and in other tissues.

scholarly journals Transcriptome Analysis Reveals the Long Intergenic Noncoding RNAs Contributed to Skeletal Muscle Differences between Yorkshire and Tibetan Pig

2020 ◽  
Author(s):  
Ziying Huang ◽  
Qianqian Li ◽  
Mengxun Li ◽  
Changchun Li
Keyword(s):  
Skeletal Muscle ◽  
Noncoding Rna ◽  
Muscle Development ◽  
Target Genes ◽  
Differential Expression Analysis ◽  
Muscle Growth ◽  
Skeletal Muscle Development ◽  
Tibetan Pig ◽  
The Difference

Abstract Background: The difference between the skeletal muscle growth rates of Western and domestic breeds is remarkable, but the potential regulatory mechanism involved is still unclear. Numerous studies have pointed out that long intergenic noncoding RNA (lincRNA) plays a key role in skeletal muscle development. This study used published Yorkshire (LW) and Tibetan pig (TP) transcriptome data to explore the possible role of lincRNA in the difference in skeletal muscle development between the two breeds. Results: Through differential expression analysis, 138 differentially expressed lincRNAs (DELs) were obtained between the two breeds, and their potential target genes (PTGs) were predicted. The results of Gene Ontology and pathway analysis revealed that PTGs are involved in multiple biological processes and pathways related to muscle development. The quantitative trait loci (QTLs) of DELs were predicted, and the results showed that most QTLs are related to muscle development. Finally, we constructed a co-expression network between muscle development related PTGs (MDRPTGs) and their corresponding DELs on the basis of their expression levels. The expression of DELs was significantly correlated with the corresponding MDRPTGs. Also, multiple MDRPTGs are involved in the key regulatory pathway of muscle fiber hypertrophy, which is the IGF-1-AKT-mTOR pathway. Conclusions: In summary, multiple lincRNAs that may cause differences in skeletal muscle development between the two breeds were identified, and their possible regulatory roles were explored. The findings of this study may provide a valuable reference for further research on the role of lincRNA in skeletal muscle development.

scholarly journals smORFunction: A Tool for Predicting Functions of Small Open Reading Frames and Microproteins

2020 ◽  
Author(s):  
Xiangwen Ji ◽  
Chunmei Cui ◽  
Qinghua Cui
Keyword(s):  
Open Reading Frames ◽  
Open Reading Frame ◽  
Biological Processes ◽  
Reading Frame ◽  
Functional Annotations ◽  
Uniprot Database ◽  
Muscle Formation ◽  
Small Open Reading Frame ◽  
Reading Frames ◽  
Small Open Reading Frames

Abstract Background Small open reading frame (smORF) is open reading frame with a length of less than 100 codons. Microproteins, translated from smORFs, have been found to participate in a variety of biological processes such as muscle formation and contraction, cell proliferation, and immune activation. Although previous studies have collected and annotated a large abundance of smORFs, functions of the vast majority of smORFs are still unknown. It is thus increasingly important to develop computational methods to annotate the functions of these smORFs. Results In this study, we collected 617,462 unique smORFs from three studies. The expression of smORF RNAs was estimated by reannotated microarray probes. Using a speed-optimized correlation algorism, the functions of smORFs were predicted by their correlated genes with known functional annotations. After applying our method to 5 known microproteins from literatures, our method successfully predicted their functions. Further validation from the UniProt database showed that at least one function of 202 out of 270 microproteins was predicted. Conclusions We developed a method, smORFunction, to provide function predictions of smORFs/microproteins in at most 265 models generated from 173 datasets, including 48 tissues/cells, 82 diseases (and normal). The tool can be available at http://www.cuilab.cn/smorfunction.

scholarly journals Male-Biased gga-miR-2954 Regulates Myoblast Proliferation and Differentiation of Chicken Embryos by Targeting YY1

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1325
Author(s):  
Xiuxue Dong ◽  
Yu Cheng ◽  
Lingyun Qiao ◽  
Xin Wang ◽  
Cuiping Zeng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Expression Profiles ◽  
Myoblast Differentiation ◽  
Mammalian Skeletal Muscle ◽  
Loss Of Function ◽  
Skeletal Muscle Development ◽  
Chicken Muscle ◽  
Proliferation And Differentiation ◽  
Myoblast Proliferation

Previous studies have shown that gga-miR-2954 was highly expressed in the gonads and other tissues of male chickens, including muscle tissue. Yin Yang1 (YY1), which has functions in mammalian skeletal muscle development, was predicted to be a target gene of gga-miR-2954. The purpose of this study was to investigate whether gga-miR-2954 plays a role in skeletal muscle development by targeting YY1, and evaluate its function in the sexual dimorphism development of chicken muscle. Here, all the temporal and spatial expression profiles in chicken embryonic muscles showed that gga-miR-2954 is highly expressed in males and mainly localized in cytoplasm. Gga-miR-2954 exhibited upregulated expression of in vitro myoblast differentiation stages. Next, through the overexpression and loss-of-function experiments performed in chicken primary myoblasts, we found that gga-miR-2954 inhibited myoblast proliferation but promoted differentiation. During myogenesis, gga-miR-2954 could suppress the expression of YY1, which promoted myoblast proliferation and inhibited the process of myoblast cell differentiation into multinucleated myotubes. Overall, these findings reveal a novel role of gga-miR-2954 in skeletal muscle development through its function of the myoblast proliferation and differentiation by suppressing the expression of YY1. Moreover, gga-miR-2954 may contribute to the sex difference in chicken muscle development.

scholarly journals smORFunction: A Tool for Predicting Functions of Small Open Reading Frames and Microproteins

2020 ◽  
Author(s):  
Xiangwen Ji ◽  
Chunmei Cui ◽  
Qinghua Cui
Keyword(s):  
Open Reading Frames ◽  
Open Reading Frame ◽  
Biological Processes ◽  
Reading Frame ◽  
Functional Annotations ◽  
Uniprot Database ◽  
Muscle Formation ◽  
Small Open Reading Frame ◽  
Reading Frames ◽  
Small Open Reading Frames

Abstract Background Small open reading frame (smORF) is open reading frame with a length of less than 100 codons. Microproteins, translated from smORFs, have been found to participate in a variety of biological processes such as muscle formation and contraction, cell proliferation, and immune activation. Although previous studies have collected and annotated a large abundance of smORFs, functions of the vast majority of smORFs are still unknown. It is thus increasingly important to develop computational methods to annotate the functions of these smORFs. Results In this study, we collected 617,462 unique smORFs from three studies. The expression of smORF RNAs was estimated by reannotated microarray probes. Using a speed-optimized correlation algorism, the functions of smORFs were predicted by their correlated genes with known functional annotations. After applying our method to 5 known microproteins from literatures, our method successfully predicted their functions. Further validation from the UniProt database showed that at least one function of 202 out of 270 microproteins was predicted. Conclusions We developed a method, smORFunction, to provide function predictions of smORFs/microproteins in at most 265 models generated from 173 datasets, including 48 tissues/cells, 82 diseases (and normal). The tool can be available at http://www.cuilab.cn/smorfunction.

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