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. 2021 Mar 7;22(5):2692.
doi: 10.3390/ijms22052692.

microRNA-mRNA Profile of Skeletal Muscle Differentiation and Relevance to Congenital Myotonic Dystrophy

Sarah U Morton  1   2 , Christopher R Sefton  3 , Huanqing Zhang  4 , Manhong Dai  4 , David L Turner  4   5 , Michael D Uhler  4   5 , Pankaj B Agrawal  1   2   6   7
Affiliations

microRNA-mRNA Profile of Skeletal Muscle Differentiation and Relevance to Congenital Myotonic Dystrophy

Sarah U Morton et al. Int J Mol Sci. .

Abstract

microRNAs (miRNAs) regulate messenger RNA (mRNA) abundance and translation during key developmental processes including muscle differentiation. Assessment of miRNA targets can provide insight into muscle biology and gene expression profiles altered by disease. mRNA and miRNA libraries were generated from C2C12 myoblasts during differentiation, and predicted miRNA targets were identified based on presence of miRNA binding sites and reciprocal expression. Seventeen miRNAs were differentially expressed at all time intervals (comparing days 0, 2, and 5) of differentiation. mRNA targets of differentially expressed miRNAs were enriched for functions related to calcium signaling and sarcomere formation. To evaluate this relationship in a disease state, we evaluated the miRNAs differentially expressed in human congenital myotonic dystrophy (CMD) myoblasts and compared with normal control. Seventy-four miRNAs were differentially expressed during healthy human myocyte maturation, of which only 12 were also up- or downregulated in CMD patient cells. The 62 miRNAs that were only differentially expressed in healthy cells were compared with differentiating C2C12 cells. Eighteen of the 62 were conserved in mouse and up- or down-regulated during mouse myoblast differentiation, and their C2C12 targets were enriched for functions related to muscle differentiation and contraction.

Keywords: congenital myotonic dystrophy; microRNA; muscle differentiation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Differentially expressed (A) miRNA and (B) mRNA at day 2 vs. day 0 (D2_D0, myoblast to early myocyte), day 5 vs. day 0 (D5_D0, myoblast to mature myocyte), and day 5 vs. day 2 (D5_D2, early myocyte to mature myocyte).
Figure 2
Figure 2
Top functional enrichments among differentially expressed mRNAs during muscle differentiation. Only the most significantly enriched term among closely related terms was included. Z-score for pathway activity is written on the relevant bar where applicable.
Figure 3
Figure 3
miRNAs are predicted to target multiple mRNAs at D2_D0 (A,B) and D5_D0 (C,D) that encode proteins related to calcium signaling (A,C) and sarcomeres (B,D).
Figure 4
Figure 4
Functional enrichment among predicted mRNA targets of myomiRs (A) and miR-503 cluster miRNAs (B) based on protein-protein interaction and gene ontology analysis. In A, red denotes proteins that contribute to positive regulation of developmental process. In B, red spheres denotes proteins that are involved in proliferation. White spheres denote proteins that lack a directional pattern of effect. Only the most significantly enriched term among closely related terms was included.
See this image and copyright information in PMC

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