Abstract
ObjectivesLong non‐coding RNAs (LncRNAs) play important roles in epigenetic regulatory function during the development processes. In this study, we found that through alternative splicing, LncRNA C130071C03Riken variants Riken‐201 (Riken‐201) and Riken‐203 (Riken‐203) are both expressed highly in brain, and increase gradually during neural differentiation. However, the function of Rik‐201 and Rik‐203 is unknown.Materials and methodsEmbryonic 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.ResultsRepression 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.ConclusionsThese 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.
Highlights
Neural differentiation is an important developmental event during gastrulation of the embryonic development.[1]
MicroRNAs are 20‐25 nucleotide non‐coding RNAs that partially bind to the mRNA 3′ untranslated regions (3′UTRs) to induce the translational repression.[17,18] miRNAs are involved in many biological and physiological processes, such as the regulation of disease formation, and embryonic development.[19,20,21,22] miRNAs are abundant in the central nervous system (CNS) and are critically involved in all stages of neural differentiation during brain development.[23,24] miR‐96 has been re‐ ported to repress neural induction from human embryonic stem cells by targeting Pax[6], the critical regulator of neural differentia‐ tion.[25]
We found that Rik‐201 and Rik‐203 were significantly higher ex‐ pressed in the mouse brain than in other tissues of E14.5 embryo
Summary
Neural differentiation is an important developmental event during gastrulation of the embryonic development.[1]. MicroRNAs (miRNAs) are 20‐25 nucleotide (nt) non‐coding RNAs that partially bind to the mRNA 3′ untranslated regions (3′UTRs) to induce the translational repression.[17,18] miRNAs are involved in many biological and physiological processes, such as the regulation of disease formation, and embryonic development.[19,20,21,22] miRNAs are abundant in the CNS and are critically involved in all stages of neural differentiation during brain development.[23,24] miR‐96 has been re‐ ported to repress neural induction from human embryonic stem cells (hESCs) by targeting Pax[6], the critical regulator of neural differentia‐ tion.[25] Whether miR‐96 regulated the neural differentiation and the regulatory mechanism remains unclear. Whether Sox[6] could be regulated by miRNAs during the neural differentiation remains unknown
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