Abstract
BackgroundThe small non-protein-coding microRNAs (miRNAs) have emerged as critical regulators of neuronal differentiation, identity and survival. To date, however, little is known about the genes and molecular networks regulated by neuronal miRNAs in vivo, particularly in the adult mammalian brain.Methodology/Principal FindingsWe analyzed whole genome microarrays from mice lacking Dicer, the enzyme responsible for miRNA production, specifically in postnatal forebrain neurons. A total of 755 mRNA transcripts were significantly (P<0.05, FDR<0.25) misregulated in the conditional Dicer knockout mice. Ten genes, including Tnrc6c, Dnmt3a, and Limk1, were validated by real time quantitative RT-PCR. Upregulated transcripts were enriched in nonneuronal genes, which is consistent with previous studies in vitro. Microarray data mining showed that upregulated genes were enriched in biological processes related to gene expression regulation, while downregulated genes were associated with neuronal functions. Molecular pathways associated with neurological disorders, cellular organization and cellular maintenance were altered in the Dicer mutant mice. Numerous miRNA target sites were enriched in the 3′untranslated region (3′UTR) of upregulated genes, the most significant corresponding to the miR-124 seed sequence. Interestingly, our results suggest that, in addition to miR-124, a large fraction of the neuronal miRNome participates, by order of abundance, in coordinated gene expression regulation and neuronal maintenance.Conclusions/SignificanceTaken together, these results provide new clues into the role of specific miRNA pathways in the regulation of brain identity and maintenance in adult mice.
Highlights
Accumulating evidence suggest that miRNAs, highly conserved small noncoding regulatory RNAs, are required for cell differentiation, identity, and maintenance [1,2]
We performed genome-wide microarrays (Affymetrix mouse exon ST 1.0) on brain tissue isolated from 9–10.5 week-old Dicer conditional knockout mice [14]
We identified 755 transcripts to be significantly (P,0.05, FDR,0.25) altered in the Dicer conditional knockout (cKO) mice when compared to controls (Figure 1A and Table S1)
Summary
Accumulating evidence suggest that miRNAs, highly conserved small noncoding regulatory RNAs, are required for cell differentiation, identity, and maintenance [1,2]. The precursor miRNA is cleaved by the ribonuclease Dicer to generate ,21 nucleotide double-stranded RNAs. The mature miRNA is loaded into the RNA-induced silencing complex (RISC), which comprises Dicer and the Argonaute (eif2c/Ago) proteins as the catalytic core [4]. The mature miRNA is loaded into the RNA-induced silencing complex (RISC), which comprises Dicer and the Argonaute (eif2c/Ago) proteins as the catalytic core [4] As part of this complex, single-stranded miRNAs target, with partial complementarity, mRNA transcripts mainly within the 39UTR leading to mRNA degradation or translational repression [5]. The small non-protein-coding microRNAs (miRNAs) have emerged as critical regulators of neuronal differentiation, identity and survival. Little is known about the genes and molecular networks regulated by neuronal miRNAs in vivo, in the adult mammalian brain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
