Transcriptome analysis of microRNAs in developing cerebral cortex of rat

Abstract

BackgroundThe morphogenesis of the cerebral cortex depends on the precise control of gene expression during development. Small non-coding RNAs, including microRNAs and other groups of small RNAs, play profound roles in various physiological and pathological processes via their regulation of gene expression. A systematic analysis of the expression profile of small non-coding RNAs in developing cortical tissues is important for clarifying the gene regulation networks mediating key developmental events during cortical morphogenesis.ResultsGlobal profiling of the small RNA transcriptome was carried out in rat cerebral cortex from E10 till P28 using next-generation sequencing technique. We found an extraordinary degree of developmental stage-specific expression of a large group of microRNAs. A group of novel microRNAs with functional hints were identified, and brain-enriched expression and Dicer-dependent production of high-abundant novel microRNAs were validated. Profound editing of known microRNAs at “seed” sequence and flanking sequence was observed, with much higher editing events detected at late postnatal stages than embryonic stages, suggesting the necessity of microRNA editing for the fine tuning of gene expression during the formation of complicated synaptic connections at postnatal stages.ConclusionOur analysis reveals extensive regulation of microRNAs during cortical development. The dataset described here will be a valuable resource for clarifying new regulatory mechanisms for cortical development and diseases and will greatly contribute to our understanding of the divergence, modification, and function of microRNAs.

Convergent microRNA actions coordinate neocortical development

“…2 % of miRNAs underwent significant changes between E11 and E13, whereas the majority of them did not change expression during this developmental time window. It should be noted, however, that some of the miRNAs found to be highly expressed between E10 and E11 in Yao’s study, such as miR-20b*, -126, -143, -183, -199a, -200b/c, -214, -222 and -292-3p, are not overlapping with those of Nielsen’s study [46, 48]. This discrepancy might be due to the different sensitivity of the methods used, to the different cell sources, or to the existence of strain-specific miRNAs.…”

MicroRNA-mediated regulation of target genes in several brain regions is correlated to both microRNA-targeting-specific promoter methylation and differential microRNA expression

“…Asterisked miRNAs appear more than once. Bold faced miRNAs were previously reported to be related to brain development/diseases [37-39]. See subsection “The selection of miRNAs that significantly regulate target genes based on multiple regression model” in Supplementary Document (see Additional file 1) for the detailed criterion of miRNAs selection.…”

MicroRNAs in neural development: from master regulators to fine-tuners

“…We refer the reader to excellent recent reviews for a detailed discussion of miRNA function in adult neurogenesis (Luikart et al, 2012;Schouten et al, 2012) and focus our discussion here on embryonic neurogenesis -a period during which many miRNAs are enriched. Indeed, the global monitoring of miRNA expression during neurogenesis in vivo has identified timespecific (Barca-Mayo and De Pietri Tonelli, 2014;Lv et al, 2014;Miska et al, 2004;Nielsen et al, 2009;Yao et al, 2012), spatially restricted (ventral midline/midbrain dopaminergic progenitor pool) (Anderegg et al, 2013) or cell type-specific (Paridaen and Huttner, 2014;Ghosh et al, 2014) miRNAs, suggesting that different sets of miRNAs might be involved in neuronal versus glial differentiation. This is supported by the finding that 116 miRNAs (out of 351) are differentially expressed in primary cultures enriched for neurons, astrocytes, oligodendrocytes and microglia (Jovicic et al, 2013).…”