Global profiling of gene expression in mouse astrocyte in response to the potential longevity determinant miR-29

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  • マウス・アストロサイトでのmiR-29依存性の遺伝子発現の網羅的解析

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Abstract

MicroRNAs (miRNAs) are an evolutionarily conserved large class of small non-coding RNAs that mediate posttranscriptional silencing of genes and influence a broad spectrum of biological processes ranging from embryonic development to organismal death. Our previous study identified the miR-29 family, three paralogous species of miR-29a/b/c, as the most predominantly expressed small RNA in aged mouse brain compared to the neonate one. Mouse brain miR-29 is highly astrocytic. Its expression is quiescent during early brain development, and then steadily increases to a plateau state around reproductive maturity. To explore the functional relevance of miR-29 expression in early life to the neural physiology of the mouse brain from the mechanistic perspective of mammalian species-specific lifespan, we here undertook a gain-of-function approach through exogenous expression of miR-29 in astrocyte from mouse fetus and surveyed the resulting alteration in both the transcriptional and translational levels. DNA microarray analyses retrieved a total of 5,589 genes showing temporal significant expression changes in the miR-29-transfected fetal astrocytes, and classified them into two gene groups: positively or negatively regulated by miR-29. Mass spectrometry (MS)-based quantification of translational products of miR-29-responsive genes identified 18 species of miR-29 target candidates. We performed functional enrichment analyses utilizing bioinformatics resources to characterize the gene sets thus identified, and found their expression trend that favor the processes for facilitating cell differentiation while supporting normal cell proliferation/survival, which is somewhat different from the functional signatures of miR-29 as observed at adult stages, implying a pleiotropic property of miR-29 depending on the developmental context. Our present results strongly suggest that miR-29 in the developing mouse brain serves as the central coordinator to shift the global gene expression toward adult phenotypes, through which ensure the programmed transition in the life course to the post-developmental/reproductive stage which has inherently been set to delimit the mouse life potential.

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