Circular RNA (circRNA) is a kind of novel endogenous noncoding RNA formed through back-splicing of mRNA precursor. The biogenesis, degradation, nucleus–cytoplasm transport, location, and even translation of circRNA are controlled by RNA-binding proteins (RBPs). Therefore, circRNAs and the chaperoned RBPs play critical roles in biological functions that significantly contribute to normal animal development and disease. In this review, we systematically characterize the possible molecular mechanism of circRNA–protein interactions, summarize the latest research on circRNA–protein interactions in muscle development and myocardial disease, and discuss the future application of circRNA in treating muscle diseases. Finally, we provide several valid prediction methods and experimental verification approaches. Our review reveals the significance of circRNAs and their protein chaperones and provides a reference for further study in this field.

Diarrhea is associated with gut microbiota, immunity, and metabolic alterations in goat kids and lambs. This study used 28 lambs (11 healthy and 17 diarrheic) and 20 goat kids (10 healthy and 10 diarrheic) to investigate the association between diarrhea occurrence and changes in gut microbiota, metabolism, and immunity in goat kids and lambs. The results revealed that Firmicutes, Proteobacteria, and Bacteroidetes were the dominant phyla in goat kids and lambs. In addition, Enterobacteriaceae and Lachnospiraceae families were identified in both diarrheic goat kids and lambs. Furthermore, functional prediction of microbiota showed that it was involved in cell motility and cancer pathways. The identified differential metabolites were implicated in the bile secretion pathway. Lambs had significant differences in immunoglobulin G (IgG), immunoglobulin M (IgM), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) compared to goat kids. IgG and IL-1β were positively correlated to Patescibacteria, Clostridiaceae, and unclassified_Muribaculaceae in both diarrheic goat kids and lambs. In addition, weighted gene co-expression network analysis (WGCNA) revealed that the MEgreen module was positively associated with IgG, IgM, IL-1β, TNF-α, and triglyceride (TG). In conclusion, our results characterized the gut microbiota, metabolism, and immune status of lambs and goat kids suffering from diarrhea.

Myogenesis is a complex process controlled by several coding and non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs) that are known to function as endogenous microRNAs (miRNAs) sponges. Cerebellar Degeneration-Related protein 1 antisense (CDR1as) is the most spotlighted circRNA that is known as an miR-7 sponge, which has bloomed circRNAs’ research in animal disease and physiology. Here, we screened for miRNAs and mRNA associated with CDR1as and further characterized their regulatory function during muscle differentiation. We found that a total of 43 miRNAs (including miR-107-3p, miR-125b-5p, miR-140-5p, miR-29a-3p, and miR-27a-3p upregulated) and 789 mRNAs (including ANGPT1, E2F2, CCN1, FGFR1, and MEF2C downregulated) were differentially expressed in goat skeletal muscle satellite cells (SMSCs). Further, knockdown of CDR1as and ANGPT1 inhibited SMSCs differentiation. miR-27a-3p was differentially upregulated after the knockdown of CDR1as in SMSCs. Overexpressed miR-27a-3p decreased SMSCs differentiation. Via RNAhybrid and luciferase, miR-27a-3p was identified to regulate ANGPT1. We discovered that miR-27a-3p has an inverse relationship with CDR1as and decreases the expression level of ANGPT1 during SMSCs differentiation. In summary, our study demonstrates that siCDR1as inhibits myoblast differentiation by downregulating ANGPT1 mRNA via miR-27a-3p in SMSCs.

Domestic animals have multiple phenotypes of skin and coat color, which arise from different genes and their products, such as proteins and metabolites responsible with melanin deposition. However, the complex regulatory network of melanin synthesis remains to be fully unraveled. Here, the skin and tongue tissues of Liangshan black sheep (black group) and Liangshan semi-fine-wool sheep (pink group) were collected, stained with hematoxylin–eosin (HE) and Masson–Fontana, and the transcriptomic and metabolomic data were further analyzed. We found a large deposit of melanin granules in the epidermis of the black skin and tongue. Transcriptome and metabolome analysis identified 744 differentially expressed genes (DEGs) and 443 differentially expressed metabolites (DEMs) between the pink and black groups. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed the DEGs and DEMs were mainly enriched in the pathways of secondary metabolic processes, melanin biosynthesis processes, melanin metabolism processes, melanosome membranes, pigment granule membranes, melanosome, tyrosine metabolism, and melanogenesis. Notably, we revealed the gene ENSARG00020006042 may be a family member of YWHAs and involved in regulating melanin deposition. Furthermore, several essential genes (TYR, TYRP1, DCT, PMEL, MLANA, SLC45A2) were significantly associated with metabolite prostaglandins and compounds involved in sheep pigmentation. These findings provide new evidence of the strong correlation between prostaglandins and related compounds and key genes that regulate sheep melanin synthesis, furthering our understanding of the regulatory mechanisms and molecular breeding of pigmentation in sheep.

The rumen is an important digestive organ of ruminants. From the fetal to adult stage, the morphology, structure and function of the rumen change significantly. However, the knowledge of the intrinsic genetic regulation of these changes is still limited. We previously reported a genome-wide expression profile of miRNAs in pre-natal goat rumens. In this study, we combined and analyzed the transcriptomes of rumen miRNAs during pre-natal (E60 and E135) and post-natal (D30 and D150) stages. A total of 66 differentially expressed miRNAs (DEMs) were identified in the rumen tissues from D30 and D150 goats. Of these, 17 DEMs were consistently highly expressed in the rumens at the pre-weaning stages (E60, E135 and D30), while down-regulated at D150. Noteworthy, annotation analysis revealed that the target genes regulated by the DEMs were mainly enriched in MAPK signaling pathway, Jak-STAT signaling pathway and Ras signaling pathway. Interestingly, the expression of miR-148a-3p was significantly high in the embryonic stage and down-regulated at D150. The potential binding sites of miR-148a-3p in the 3′-UTR of QKI were predicted by the TargetScan and verified by the dual luciferase report assay. The co-localization of miR-148a-3p and QKI through in situ hybridization was observed in the rumen tissues but not in the intestinal tracts. Moreover, the expression of miR-148a-3p in the epithelium was significantly higher than that in the other layers of the rumen, suggesting that miR-148a-3p is involved in the development of the rumen epithelial cells by targeting QKI. Subsequently, miR-148a-3p inhibitor was found to induce the proliferation of GES-1 cells. Taken together, our study identified DEMs involved in the development of the rumen and provides insights into the regulation mechanism of rumen development in goats.

The development of mammalian skeletal muscle is a highly complex process involving multiple molecular interactions. As a prevalent RNA modification, N6-methyladenosine (m⁶A) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains unclear how m⁶A participates in the development of goat muscle. In this study, methyltransferase 3 (METTL3) was significantly enriched in goat longissimus dorsi (LD) tissue. In addition, the global m⁶A modification level and differentiation of skeletal muscle satellite cells (MuSCs) were regulated by METTL3. By performing mRNA-seq analysis, 8050 candidate genes exhibited significant changes in expression level after the knockdown of METTL3 in MuSCs. Additionally, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that myocyte enhancer factor 2c (MEF2C) mRNA contained m⁶A modification. Further experiments demonstrated that METTL3 enhanced the differentiation of MuSCs by upregulating m⁶A levels and expression of MEF2C. Moreover, the m⁶A reader YTH N6-methyladenosine RNA binding protein C1 (YTHDC1) was bound and stabilized to MEF2C mRNA. The present study reveals that METTL3 enhances myogenic differentiation in MuSCs by regulating MEF2C and provides evidence of a post-transcriptional mechanism in the development of goat skeletal muscle.