PMID- 24324399 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20131210 LR - 20211021 IS - 1662-5099 (Print) IS - 1662-5099 (Electronic) IS - 1662-5099 (Linking) VI - 6 DP - 2013 TI - A comprehensive characterization of the nuclear microRNA repertoire of post-mitotic neurons. PG - 43 LID - 10.3389/fnmol.2013.00043 [doi] LID - 43 AB - 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. FAU - Khudayberdiev, Sharof A AU - Khudayberdiev SA AD - Biochemisch-Pharmakologisches Centrum, Institut fur Physiologische Chemie, Philipps-Universitat Marburg Marburg, Germany. FAU - Zampa, Federico AU - Zampa F FAU - Rajman, Marek AU - Rajman M FAU - Schratt, Gerhard AU - Schratt G LA - eng PT - Journal Article DEP - 20131126 PL - Switzerland TA - Front Mol Neurosci JT - Frontiers in molecular neuroscience JID - 101477914 PMC - PMC3840315 OTO - NOTNLM OT - deep sequencing OT - isomiR OT - miRNA OT - microarray OT - neuronal development OT - plasticity EDAT- 2013/12/11 06:00 MHDA- 2013/12/11 06:01 PMCR- 2013/01/01 CRDT- 2013/12/11 06:00 PHST- 2013/09/16 00:00 [received] PHST- 2013/11/07 00:00 [accepted] PHST- 2013/12/11 06:00 [entrez] PHST- 2013/12/11 06:00 [pubmed] PHST- 2013/12/11 06:01 [medline] PHST- 2013/01/01 00:00 [pmc-release] AID - 10.3389/fnmol.2013.00043 [doi] PST - epublish SO - Front Mol Neurosci. 2013 Nov 26;6:43. doi: 10.3389/fnmol.2013.00043. eCollection 2013.