Dataset Information

MiR-29a regulates the proliferation and differentiation of retinal progenitors by targeting Rbm8a.

ABSTRACT: During development, tight regulation of the expansion of retinal progenitor cells (RPCs) and their differentiation into neuronal and glial cells is important for retinal formation and function. Our study demonstrated that microRNA (miR)-29a modulated the proliferation and differentiation of RPCs by suppressing RBM8A (one of the factors in the exon junction complex). Particularly, overexpression of miR-29a reduced RPC proliferation but accelerated RPC differentiation. By contrast, reduction of endogenous miR-29a elicited the opposite effects. Overexpression of miR-29a repressed the translation of Rbm8a, thus negatively regulating RPC proliferation and promoting the neuronal and glial differentiation of RPCs, and knockdown of endogenous Rbm8a phenocopied the observed effects of miR-29a overexpression. Furthermore, a luciferase reporter assay showed that miR-29a directly interacted with the Rbm8a mRNA 3'UTR, which indicated that Rbm8a is the direct target of miR-29a. To further verify the result, co-overexpression of the Rbm8a 3' UTR-wt (plasmids into which the Rbm8a 3' UTR sequence had been introduced) and miR-29a in RPCs rescued the phenotype associated with miR-29a overexpression, reversing the promotion of differentiation and inhibition of proliferation. These results show a novel mechanism by which miR-29a regulates the proliferation and differentiation of RPCs through Rbm8a.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5458264 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-29a regulates the proliferation and differentiation of retinal progenitors by targeting Rbm8a.

Zhang Yi Y Shen Bingqiao B Zhang Dandan D Wang Yuyao Y Tang Zhimin Z Ni Ni N Jin Xiaoliang X Luo Min M Sun Hao H Gu Ping P

Oncotarget 20170501 19

During development, tight regulation of the expansion of retinal progenitor cells (RPCs) and their differentiation into neuronal and glial cells is important for retinal formation and function. Our study demonstrated that microRNA (miR)-29a modulated the proliferation and differentiation of RPCs by suppressing RBM8A (one of the factors in the exon junction complex). Particularly, overexpression of miR-29a reduced RPC proliferation but accelerated RPC differentiation. By contrast, reduction of en ...[more]

PMID: 28404883

Similar Datasets

Project description:BackgroundNonsense mediated mRNA decay (NMD) is an RNA surveillance mechanism that controls RNA stability and ensures the speedy degradation of erroneous and unnecessary transcripts. This mechanism depends on several core factors in the exon junction complex (EJC), eIF4A3, RBM8a, Magoh, and BTZ, as well as peripheral factors to distinguish premature stop codons (PTCs) from normal stop codons in transcripts. Recently, emerging evidence has indicated that NMD factors are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). However, the mechanism in which these factors control embryonic brain development is not clear.ResultWe found that RBM8a is critical for proliferation and differentiation in cortical neural progenitor cells (NPCs). RBM8a is highly expressed in the subventricular zone (SVZ) of the early embryonic cortex, suggesting that RBM8a may play a role in regulating NPCs. RBM8a overexpression stimulates embryonic NPC proliferation and suppresses neuronal differentiation. Conversely, knockdown of RBM8a in the neocortex reduces NPC proliferation and promotes premature neuronal differentiation. Moreover, overexpression of RBM8a suppresses cell cycle exit and keeps cortical NPCs in a proliferative state. To uncover the underlying mechanisms of this phenotype, genome-wide RNAseq was used to identify potential downstream genes of RBM8a in the brain, which have been implicated in autism and neurodevelopmental disorders. Interestingly, autism and schizophrenia risk genes are highly represented in downstream transcripts of RBM8a. In addition, RBM8a regulates multiple alternative splicing genes and NMD targets that are implicated in ASD. Taken together, this data suggests a novel role of RBM8a in the regulation of neurodevelopment.ConclusionsOur studies provide some insight into causes of mental illnesses and will facilitate the development of new therapeutic strategies for neurodevelopmental illnesses.

Project description:ObjectiveTo investigate the modulation of microRNAs (miRNAs) upon the neuronal differentiation of mesenchymal stem cells (MSCs) through targeting RE-1 Silencing Factor (REST), a mature neuronal gene suppressor in neuronal and un-neuronal cells.MethodsRat bone marrow derived-MSCs were induced into neuron-like cells (MSC-NCs) by DMSO and BHA in vitro. The expression of neuron specific enolase (NSE), microtubule-associated protein tau (Tau), REST and its target genes, including synaptosomal-associated protein 25 (SNAP25) and L1 cell adhesion molecular (L1CAM), were detected in MSCs and MSC-NCs. miRNA array analysis was conducted to screen for the upregulated miRNAs after neuronal differentiation. TargetScan was used to predict the relationship between these miRNAs and REST gene, and dual luciferase reporter assay was applied to validate it. Gain and loss of function experiments were used to study the role of miR-29a upon neuronal differentiation of MSCs. The knockdown of REST was conducted to show that miR-29a affected this process through targeting REST.ResultsMSCs were induced into neuron-like cells which presented neuronal cell shape and expressed NSE and Tau. The expression of REST declined and the expression of SNAP25 and L1CAM increased upon the neuronal differentiation of MSCs. Among 14 upregulated miRNAs, miR-29a was validated to target REST gene. During the neuronal differentiation of MSCs, miR-29a inhibition blocked the downregulation of REST, as well as the upregulation of SNAP25, L1CAM, NSE and Tau. REST knockdown rescued the effect of miR-29a inhibition on the expression of NSE and Tau. Meanwhile, miR-29a knockin significantly decreased the expression of REST and increased the expression of SNAP25 and L1CMA in MSCs, but did not significantly affect the expression of NSE and Tau.ConclusionmiR-29a regulates neurogenic markers through targeting REST in mesenchymal stem cells, which provides advances in neuronal differentiation research and stem cell therapy for neurodegenerative diseases.

Dataset Information

MiR-29a regulates the proliferation and differentiation of retinal progenitors by targeting Rbm8a.

Publications

miR-29a regulates the proliferation and differentiation of retinal progenitors by targeting Rbm8a.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets