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Circular RNAs (circRNAs) are an evolutionarily conserved novel class of non-coding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome, originally believed to be aberrant RNA splicing by-products with decreased functionality. However, recent advances in high-throughput genomic technology have allowed circRNAs to be characterized in detail and revealed their role in controlling various biological and molecular processes, the most essential being gene regulation. Because of the structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA biology. Compared to the linear RNA, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming a covalently closed loop structure missing 3′ poly-(A) tail or 5′ cap, rendering them immune to exonuclease-mediated degradation. Emerging research has identified multifaceted roles of circRNAs as miRNA and RNA binding protein (RBP) sponges and transcription, translation, and splicing event regulators. CircRNAs have been involved in many human illnesses, including cancer and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, due to their aberrant expression in different pathological conditions. The functional versatility exhibited by circRNAs enables them to serve as potential diagnostic or predictive biomarkers for various diseases. This review discusses the properties, characterization, profiling, and the diverse molecular mechanisms of circRNAs and their use as potential therapeutic targets in different human malignancies.

Being the center of the hypothalamus-pituitary-ovary (HPO) axis, the pituitary plays a key role in the onset of puberty. Recent studies show that circular RNAs (circRNAs) can perform as miRNA sponges to regulate development in animals. However, the function of pituitary-derived circRNAs in first estrus remains unclear in pigs. In this study, we performed a genome-wide identification and characterization of circRNAs using pituitaries from Landrace × Yorkshire crossbred pigs at three stages: pre-, in-, and post-puberty, to describe such pituitary-derived circRNAs in pigs. A total of 5148 circRNAs were found in the gilts' pituitaries, averaging 18 682 bp in genomic distance, which consisted of approximately 91% exonic, 6% intergenic, and 3% intronic circRNAs. Furthermore, 158 novel circRNAs were identified for the first time and classified as putative pituitary-specific circRNAs. Their expression levels during the onset of puberty, significantly exceeded those of the other circRNAs, and the parental genes of these putative pituitary-specific circRNAs were enriched in “ssc04917: prolactin signaling pathway,” “ssc04080: neuroactive ligand-receptor interaction,” and “ssc04728: dopaminergic synapse” pathways, all of which were consistent with pituitary functioning. Additionally, 17 differentially regulated circRNAs were found and investigated for their potential interaction with miRNAs, along with genes, by constructing a circRNA-targeted miRNA-gene network. Taken together, these results provide new insight into the circRNA-mediated timing of puberty in gilts at the pituitary level.

Being the center of the hypothalamus-pituitary-ovary (HPO) axis, the pituitary plays a key role in the onset of puberty. Recent studies show that circular RNAs (circRNAs) can perform as miRNA sponges to regulate development in animals. However, the function of pituitary-derived circRNAs in first estrus remains unclear in pigs. In this study, we performed a genome-wide identification and characterization of circRNAs using pituitaries from Landrace × Yorkshire crossbred pigs at three stages: pre-, in-, and post-puberty, to describe such pituitary-derived circRNAs in pigs. A total of 5148 circRNAs were found in the gilts' pituitaries, averaging 18 682 bp in genomic distance, which consisted of approximately 91% exonic, 6% intergenic, and 3% intronic circRNAs. Furthermore, 158 novel circRNAs were identified for the first time and classified as putative pituitary-specific circRNAs. Their expression levels during the onset of puberty, significantly exceeded those of the other circRNAs, and the parental genes of these putative pituitary-specific circRNAs were enriched in "ssc04917: prolactin signaling pathway," "ssc04080: neuroactive ligand-receptor interaction," and "ssc04728: dopaminergic synapse" pathways, all of which were consistent with pituitary functioning. Additionally, 17 differentially regulated circRNAs were found and investigated for their potential interaction with miRNAs, along with genes, by constructing a circRNA-targeted miRNA-gene network. Taken together, these results provide new insight into the circRNA-mediated timing of puberty in gilts at the pituitary level. [ABSTRACT FROM AUTHOR]

The specification of motor neuron (MN) subtypes and columnar organization in developing spinal cord is controlled by multiple transcription factors. FoxP1 drives specification of lateral motor neuron (LMN) subtypes, and we demonstrated in our previous work that FoxP1 expression levels are regulated by the microRNA miR-9. Here we show that ectopic FoxP1 expression can rescue altered LMN development caused by miR-9 over-expression, demonstrating that FoxP1 is the critical interaction partner for miR-9 in LMN development. Moreover, we have optimized this technique, called a miRNA sponge, to permit easy discovery of the role of individual miRNA in vivo using a loss-of-function approach. We here show that narrow spacing between binding sites and inclusion of a coding gene, and optimizing the number of miRNA binding sites can significantly increase the blocking ability of a sponge. We go on to show that a miR-9 sponge reduces detectable miR-9 in the ventral horn, preventing miR-9 silencing of FoxP1 in vivo, and in turn modifies MN subtypes in the spinal cord. Our designs for optimized sponges provide a knockdown tool that is ready to be used to study the function of miRNA in vivo, and in particular for generating transgenic animal models.