Circular RNA (circRNA) is a novel class of non-coding RNA generated by pre-mRNA back splicing, which is characterized by a closed-loop structure. Although circRNAs were firstly reported decades ago, their regulatory roles have not been discovered until recently. In this review, we discussed the putative biogenesis pathways and regulatory functions of circRNAs. Recent studies showed that circRNAs are abundant in skeletal muscle tissue, and their expression levels are regulated during muscle development and aging. We, thus, characterized the expression profile of circRNAs in skeletal muscle and discussed regulatory functions and mechanism-of-action of specific circRNAs in myogenesis. The future investigation into the roles of circRNAs in both physiological and pathological conditions may provide novel insights in skeletal muscle development and provide new therapeutic strategies for muscular diseases.

The emerging data indicates that non-coding RNAs (ncRNAs) epresent more than the “junk sequences” of the genome. Both miRNAs and long non-coding RNAs (lncRNAs) are involved in fundamental biological processes, and their deregulation may lead to oncogenesis and other diseases. As an important RNA-binding protein (RBP), heterogeneous nuclear ribonucleoprotein K (hnRNPK) is known to regulate gene expression through the RNA-binding domain involved in various pathways, such as transcription, splicing, and translation. HnRNPK is a highly conserved gene that is abundantly expressed in mammalian cells. The interaction of hnRNPK and ncRNAs defines the novel way through which ncRNAs affect the expression of protein-coding genes and form autoregulatory feedback loops. This review summarizes the interactions of hnRNPK and ncRNAs in regulating gene expression at transcriptional and post-transcriptional levels or by changing the genomic structure, highlighting their involvement in carcinogenesis, glucose metabolism, stem cell differentiation, virus infection and other cellular functions. Drawing connections between such discoveries might provide novel targets to control the biological outputs of cells in response to different stimuli.

HnRNPK is a heterogeneous nuclear ribonucleoprotein (hnRNP) that has been firmly implicated in transcriptional and post-transcriptional regulation. However, the molecular mechanisms by which hnRNPK orchestrates transcriptional or post-transcriptional regulation are not well understood due to early embryonic lethality in homozygous knockout mice, especially in a tissue-specific context. Strikingly, in this study, we demonstrated that hnRNPK is strongly expressed in the mouse testis and mainly localizes to the nucleus in spermatogonia, spermatocytes, and round spermatids, suggesting an important role for hnRNPK in spermatogenesis. Using a male germ cell-specific hnRNPK-depleted mouse model, we found that it is critical for testicular development and male fertility. The initiation of meiosis of following spermatogenesis was not affected in Hnrnpk cKO mice, while most germ cells were arrested at the pachytene stage of the meiosis and no mature sperm were detected in epididymides. The further RNA-seq analysis of Hnrnpk cKO mice testis revealed that the deletion of hnRNPK disturbed the expression of genes involved in male reproductive development, among which the meiosis genes were significantly affected, and Hnrnpk cKO spermatocytes failed to complete the meiotic prophase. Together, these results identify hnRNPK as an essential regulator of spermatogenesis and male fertility.