Dynamic Roles of microRNAs in Neurogenesis

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level by mediating mRNA degradation or translational inhibition. MiRNAs are implicated in many biological functions, including neurogenesis. It has been shown that miRNAs regulate multiple steps of neurogenesis, from neural stem cell proliferation to neuronal differentiation and maturation. MiRNAs execute their functions in a dynamic and context-dependent manner by targeting diverse downstream target genes, from transcriptional factors to epigenetic regulators. Identifying context-specific target genes is instrumental for understanding the roles that miRNAs play in neurogenesis. This review summarizes our current state of knowledge on the dynamic roles that miRNAs play in neural stem cells and neurogenesis.

MicroRNAs: Small molecules with big roles in neurodevelopment and diseases

“…These mature miRNAs are then loaded into the RNA-induced silencing complex (RISC), a ribonucleoprotein complex that is composed of the human immunodeficiency virus transactivating response RNA-binding protein (TRBP), Argonaute 2 (Ago2), and Dicer, to bind to the target mRNA to modulate gene expression (Bartel, 2004;Kim, 2005). miRNAs have been shown to regulate a variety of biological processes, including development, cell proliferation and fate specification, growth control, and apoptosis (Gao, 2010;Lang and Shi, 2012;Li and Jin, 2010;Shi et al, 2010;Stefani and Slack, 2008). Extensive studies have implicated miRNAs in the regulation of brain development and Experimental Neurology 268 (2015) [46][47][48][49][50][51][52][53] neurogenesis (Kosik, 2006;Kosik and Krichevsky, 2005;Lang and Shi, 2012;Li and Jin, 2010;Shi et al, 2008Shi et al, , 2010.…”

Unlocking epigenetic codes in neurogenesis

“…One strand of mature miRNA integrates into RNA-induced silencing complex (RISC), which includes Argonaute (AGOs) and GW182 proteins, and silences its mRNA targets based on imperfect base pair matching (Rana 2007;Hutvagner and Simard 2008;Jinek and Doudna 2009;Ameres and Zamore 2013). The roles of specific miRNAs in neurogenesis have been reviewed extensively elsewhere (Liu and Zhao 2009;Li and Jin 2010;Shi et al 2010;Kawahara et al 2012;Lang and Shi 2012;Singh et al 2014), so we only focus on the latest developments in miRNA biogenesis, function, and cross-talk with other epigenetic mechanisms for their potential impact on neurogenesis.…”

MicroRNAs as novel regulators of stem cell fate

“…The differentiation of NSCs is tightly associated with multiple signaling pathways: the Wnt signaling pathway regulates NSC proliferation and differentiation [95] , the transcription factors Neurog2 and Tbr2 are linked to NSC differentiation [96] ; the orphan nuclear receptor TLX is necessary for adult NSC proliferation [97] ; and the methyl CpG binding protein 2 (MeCP2), methyl-CpG binding protein 1 (MBD1), and histone-lysine N-methyltransferase Ezh2 are related to adult neurogenesis [98,99] . In the mammalian brain, some miRNAs expression is tissue-specific, such as the let-7 family, miR-124, and miR-9, which regulate neurogenesis [100,101] . Brain-specific miR-124 is upregulated during CNS development and the neuronal differentiation of the adult subventricular zone (SVZ) [102,103] .…”