Conclusions
These findings identify the functional role of Rik-201 and Rik-203 in facilitating neural differentiation and further brain development, and elucidate the underlying miRNAs-Sox6-associated molecular mechanisms.
Methods
Embryonic stem cells (ESCs); RNA sequencing; gene expression of mRNAs, LncRNAs and miRNAs; over-expression and RNA interference of genes; flow cytometry; real-time quantity PCR; and Western blot were used in the studies. RNA pull-down assay and PCR were employed to detect any miRNA that attached to Rik-201 and Rik-203. The binding of miRNA with mRNA of Sox6 was presented by the luciferase assay.
Results
Repression of Rik-201 and Rik-203 inhibited neural differentiation from mouse embryonic stem cells. Moreover, Rik-201 and Rik-203 functioned as the competing endogenous RNA (ceRNA) to repress the function of miR-96 and miR-467a-3p, respectively, and modulate the expression of Sox6 to further regulate neural differentiation. Knockout of the Rik-203 and Rik-201 induced high ratio of brain developmental retardation. Further we found that C/EBPβ might potentially activated the transcription of Rik-201 and Rik-203. Conclusions: These findings identify the functional role of Rik-201 and Rik-203 in facilitating neural differentiation and further brain development, and elucidate the underlying miRNAs-Sox6-associated molecular mechanisms.