NCBI Summary:
microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
General function
RNA metabolism, RNA processing
Comment
Cellular localization
Comment
Ovarian function
Follicle atresia, Steroid metabolism
Comment
miR-1275 controls granulosa cell apoptosis and estradiol synthesis by impairing LRH-1/CYP19A1 axis. Liu J et al. (2018) miR-1275 is one of the microRNAs (miRNAs) that are differentially expressed during follicular atresia in pig ovaries, as identified by a miRNA microarray assay in our previous study. However, its functions in follicular atresia remain unknown. In this study, we showed that miR-1275 promoted early apoptosis of porcine granulosa cells (pGCs) and the initiation of follicular atresia and inhibited E2 release and mRNA and protein expression of CYP19A1, the key gene in E2 production. Bioinformatics and luciferase reporter assays revealed that LRH-1, not CYP19A1, is a direct functional target of miR-1275. In vitro overexpression and knockdown experiments showed that LRH-1 significantly repressed apoptosis and induced E2 secretion and CYP19A1 expression in pGCs. LRH-1, whose expression was regulated by miR-1275, prevented apoptosis in pGCs. Furthermore, luciferase and chromatin immunoprecipitation assays demonstrated that LRH-1 protein bound to the CYP19A1 promoter and increased its activity. Our findings suggest that miR-1275 plays an important role in pGC apoptosis and the initiation of follicular atresia via down-regulating LRH-1 expression by directly targeting its 3'UTR, thereby inhibiting the interaction of LRH-1 protein with the CYP19A1 promoter, and repressing E2 synthesis.//////////////////