Identification of MyoD-Responsive Transcripts Reveals a Novel Long Non-coding RNA (lncRNA-AK143003) that Negatively Regulates Myoblast Differentiation

Abstract

Myogenic differentiation factor (MyoD) is a master transcription factor in muscle development and differentiation. Although several long non-coding RNAs (lncRNAs) linked to MyoD have been found to influence muscle development, the functions of many lncRNAs have not been explored. Here we utilized lncRNA and mRNA microarray analysis to identify potential lncRNAs regulated by MyoD in muscle cells. A total of 997 differentially expressed lncRNAs (335 up-regulated and 662 down-regulated) and 1,817 differentially expressed mRNAs (148 up-regulated and 1,669 down-regulated) were identified after MyoD knockdown in C2C12 cells. Functional predictions suggested that most lncRNAs are involved in the biological pathways related to muscle differentiation and cell cycle with co-expressed genes. To gain further insight into the MyoD-mediated lncRNA expression in muscle differentiation, tissue expression profiles and MyoD overexpression were performed, and we found one of the candidate lncRNAs-AK143003 was significantly regulated by MyoD. Further analyses showed its noncoding ability and cytoplasmic localisation. Silencing of AK143003 stimulated the accumulation of myogenic marker genes, whereas AK143003 overexpression led to their decreased synthesis. This study identified a multitude of MyoD-mediated lncRNAs for further investigation and identified a novel lncRNA, lnc-AK143003, which plays a role in controlling muscle differentiation.

Study on the transcriptional regulatory mechanism of the MyoD1 gene in Guanling bovine

“…The MyoD gene family (MyoD1, Myf5, MyoG, and Myf6) has been shown to act as a key regulator that controls the expression of specic proteins in the proliferation and differentiation of muscle cells. [8][9][10][11]18,27 Among them, MyoD1 plays an important role in muscle growth in the transcriptional regulation of muscle-specic genes, 38 while Myf6 (MRF4) primarily functions in a downstream role in myogenesis, including myober formation 19,39 and the maintenance of the muscle phenotype. 39 The Myf6 and MyoD1 promoters are regulated quite differently, leading to opposite roles of MRF4 and MyoD in cell proliferation and myogenic differentiation, 40 in which MyoD is a potential negative intercessor of MRF4 in regulating the cell cycle.…”

“…[4][5][6] Several transcriptional regulatory factors, including myoblast determination protein family members, are believed to act as terminal effectors of signaling cascades and to produce appropriate developmental stage-specic transcripts, regulating the development and growth of skeletal muscle. 7 Skeletal myogenesis is regulated by the MyoD protein family, which includes four myogenic regulatory factors (MRFs) [8][9][10][11] that belong to a family of muscle-specic basic helix-loop-helix (bHLH) transcription factors: myogenic differentiation (MyoD), 12 myogenic factor 5 (Myf5), 13 myogenin (MyoG), 14 and myogenic regulatory factor 4 (MRF4, also known as Mrf6). 15 Among the MRFs, the determination factor Myf5 is expressed before adoption of the myogenic fate.…”

SQLEPromotes Differentiation and Apoptosis of Bovine Skeletal Muscle-Derived Mesenchymal Stem Cells

“…Although our results are preliminary, the effect that we observed from overexpression of SQLE on differentiation of muscle cells indicates that this type of bio-technological manipulation may offer an attractive approach to breeders and other technologists seeking to improve meat production from cattle (Guo et al, 2017). Our results demonstrate several clear influences for SQLE relating to differentiation and proliferation in bovine skeletal muscle-derived MSCs.…”

“…Nowadays, the development of biomultiomics is very rapid, which provides us with advantageous methods and technical means for further exploring the mechanism of DNA methylation, histone modification (Bodega et al, 2017;Creyghton et al, 2010;Yan et al, 2016), lncRNAs (Butchart et al, 2016;Guo et al, 2017;Jin et al, 2017), and circRNAs expression in the regulation of muscle formation of bovine skeletal muscle MSCs by SQLE (Cherubini et al, 2019;Legnini et al, 2017). Then, we will use our previous research results, combining with CRISPR/Cas9 technology to produce SQLE gene-edited animals (Hryhorowicz et al, 2017;J and Das, 2019), and verify the regulatory role of SQLE on animal production performance.…”

LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of Endothelial Progenitor Cells

“…Accumulating evidence suggests that lncRNAs is tissue-specific and differentially expressed across varying stages during cell differentiation [26, 45]. Furthermore, emerging findings from Zhu et al have pointed out that the bone development and remodeling processes are regulated by lncRNAs [46].…”