A comprehensive characterization of the nuclear microRNA repertoire of post-mitotic neurons

MicroRNAs (miRNAs) are small non-coding RNAs with important functions in the development and plasticity of post-mitotic neurons. In addition to the well-described cytoplasmic function of miRNAs in post-transcriptional gene regulation, recent studies suggested that miRNAs could also be involved in tr...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2013-01, Vol.6, p.43-43
Main Authors: Khudayberdiev, Sharof A, Zampa, Federico, Rajman, Marek, Schratt, Gerhard
Format: Article
Language:English
Subjects:
Biosynthesis
Cancer
Deep sequencing
Developmental plasticity
DNA methylation
DNA microarrays
Epigenetics
Fluorescence in situ hybridization
Gene expression
Gene regulation
Genomes
Guanine
Homogenization
isomiR
Localization
Microarray
MicroRNAs
miRNA
Neurogenesis
neuronal development
Neurons
Neuroscience
Non-coding RNA
Nucleotides
Penicillin
plasticity
Post-transcription
Proteins
Ribosomal DNA
RNA polymerase
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Summary:MicroRNAs (miRNAs) are small non-coding RNAs with important functions in the development and plasticity of post-mitotic neurons. In addition to the well-described cytoplasmic function of miRNAs in post-transcriptional gene regulation, recent studies suggested that miRNAs could also be involved in transcriptional and post-transcriptional regulatory processes in the nuclei of proliferating cells. However, whether miRNAs localize to and function within the nucleus of post-mitotic neurons is unknown. Using a combination of microarray hybridization and small RNA deep sequencing, we identified a specific subset of miRNAs which are enriched in the nuclei of neurons. Nuclear enrichment of specific candidate miRNAs (miR-25 and miR-92a) could be independently validated by Northern blot, quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH). By cross-comparison to published reports, we found that nuclear accumulation of miRNAs might be linked to a down-regulation of miRNA expression during in vitro development of cortical neurons. Importantly, by generating a comprehensive isomiR profile of the nuclear and cytoplasmic compartments, we found a significant overrepresentation of guanine nucleotides (nt) at the 3'-terminus of nuclear-enriched isomiRs, suggesting the presence of neuron-specific mechanisms involved in miRNA nuclear localization. In conclusion, our results provide a starting point for future studies addressing the nuclear function of specific miRNAs and the detailed mechanisms underlying subcellular localization of miRNAs in neurons and possibly other polarized cell types.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2013.00043