Politz, J.C., Zhang, F. & Pederson, T. MicroRNA-206 colocalizes with ribosome-rich regions in both the nucleolus and cytoplasm of rat myogenic cells. Proc. Natl. Acad. Sci. USA 103, 18957-18962

Department of Biochemistry and Molecular Pharmacology and Program in Cell Dynamics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2007; 103(50):18957-62. DOI: 10.1073/pnas.0609466103
Source: PubMed


MicroRNAs are small, approximately 21- to 24-nt RNAs that have been found to regulate gene expression. miR-206 is a microRNA that is expressed at high levels in Drosophila, zebrafish, and mouse skeletal muscle and is thought to be involved in the attainment and/or maintenance of the differentiated state. We used locked nucleic acid probes for in situ hybridization analysis of the intracellular localization of miR-206 during differentiation of rat myogenic cells. Like most microRNAs, which are presumed to suppress translation of target mRNAs, we found that miR-206 occupies a cytoplasmic location in cultured myoblasts and differentiated myotubes and that its level increases in myotubes over the course of differentiation, consistent with previous findings in muscle tissue in vivo. However, to our surprise, we also observed miR-206 to be concentrated in nucleoli. A probe designed to be complementary to the precursor forms of miR-206 gave no nucleolar signal. We characterized the intracellular localization of miR-206 at higher spatial resolution and found that a substantial fraction colocalizes with 28S rRNA in both the cytoplasm and the nucleolus. miR-206 is not concentrated in either the fibrillar centers of the nucleolus or the dense fibrillar component, where ribosomal RNA transcription and early processing occur, but rather is localized in the granular component, the region of the nucleolus where final ribosome assembly takes place. These results suggest that miR-206 may associate both with nascent ribosomes in the nucleolus and with exported, functional ribosomes in the cytoplasm.

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    • "However, recent studies also demonstrate roles for miRNAs in epigenetic modifications. Several studies described the localization and enrichment of certain miRNAs in the nucleus of different tissues or cells, such as miR-29b in HeLa cell nuclei and miR-206 in rat myogenic cell nuclei, suggesting a nuclear function for miRNAs, apart from their canonical roles in the cytoplasm (Hwang et al., 2007; Liao et al., 2010; Politz et al., 2006). Although there is no direct evidence for which protein can transport mature miRNA from the cytoplasm to the nucleus, some studies identified exportin-1 (Castanotto et al., 2009) and importin-8 (Wei et al., 2014; Weinmann et al., 2009) as possible transporters. "
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    ABSTRACT: Information is rapidly accumulating regarding the role of miRNAs as key regulators of immune system development and function. It is also increasingly evident that miRNAs play an important role in host-pathogen interactions through regulation of both innate and acquired immune responses. Little is known, however, about the specific role of miRNAs in regulating normal development of the mucosal immune system, especially during the neonatal period. Furthermore, there is limited knowledge regarding the possible role the commensal microbiome may play in regulating mucosal miRNAs expression, although evidence is emerging that a variety of enteric pathogens influence miRNA expression. The current review focuses on recent information that miRNAs play an important role in regulating early development of the bovine mucosal immune system. A possible role for the commensal microbiome in regulating mucosal development by altering miRNA expression is also discussed. Finally, we explore the potential advantages of using the newborn calf as a model to determine how interactions between developmental programming, maternal factors in colostrum, and colonization of the gastrointestinal tract by commensal bacteria may alter mucosal miRNA expression and immune development. Identifying the key factors that regulate mucosal miRNA expression is critical for understanding how the balance between protective immunity and inflammation is maintained to ensure optimal gastrointestinal tract function and health of the whole organism. Copyright © 2014 Elsevier Ltd. All rights reserved.
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    • "Other examples of miRNAs found in the nucleus are miR-709, miR-690, miR-30e (Tang et al., 2012), and miR-122 (Földes-Papp et al., 2009). miRNAs can also be found in the nucleolus as precursor forms, like miR-494 and miR-664, and as mature miRNAs, like miR-21, miR-1, miR-351, miR-206 (Politz et al., 2006, 2009), and miR-320 (Marcon et al., 2008). Another intriguing subcellular localization of miRNAs is mitochondria, where they may modulate apoptosis processes in a coordinated way (Kren et al., 2009). "
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    ABSTRACT: Microribonucleic acids, best known as microRNAs or miRNAs, are small, non-coding RNAs with important regulatory roles in eukaryotic cells. Here, I present a broad review on highly relevant but generally non-depicted features of miRNAs, among which stand out the non-conventional miRNA seed sites, the unusual messenger RNA (mRNA) target regions, the non-canonical miRNA-guided mechanisms of gene expression regulation, and the recently identified new class of miRNA ligands. Furthermore, I address the miRNA uncommon genomic location, transcription, and subcellular localization. Altogether, these unusual features and roles place the miRNA system as a very diverse, complex, and intriguing biological mechanism.
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    • "The RNase P RNA assists in the 5′ processing of tRNA in the nucleolus [14]. At least one microRNA (miRNA) has been reported in the nucleolus of rat myoblasts [15], [16], and several nucleolar miRNAs were demonstrated in HeLa cells in a recent study [17]. Besides rRNA and ribosome biogenesis, a number of other functions that involve RNP assemblies have been associated with the nucleolus. "
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    ABSTRACT: Small non-coding RNAs represent RNA species that are not translated to proteins, but which have diverse and broad functional activities in physiological and pathophysiological states. The knowledge of these small RNAs is rapidly expanding in part through the use of massive parallel (deep) sequencing efforts. We present here the first deep sequencing of small RNomes in subcellular compartments with particular emphasis on small RNAs (sRNA) associated with the nucleolus. The vast majority of the cellular, cytoplasmic and nuclear sRNAs were identified as miRNAs. In contrast, the nucleolar sRNAs had a unique size distribution consisting of 19-20 and 25 nt RNAs, which were predominantly composed of small snoRNA-derived box C/D RNAs (termed as sdRNA). Sequences from 47 sdRNAs were identified, which mapped to both 5' and 3' ends of the snoRNAs, and retained conserved box C or D motifs. SdRNA reads mapping to SNORD44 comprised 74% of all nucleolar sdRNAs, and were confirmed by Northern blotting as comprising both 20 and 25 nt RNAs. A novel 120 nt SNORD44 form was also identified. The expression of the SNORD44 sdRNA and 120 nt form was independent of Dicer/Drosha-mediated processing pathways but was dependent on the box C/D snoRNP proteins/sno-ribonucleoproteins fibrillarin and NOP58. The 120 nt SNORD44-derived RNA bound to fibrillarin suggesting that C/D sno-ribonucleoproteins are involved in regulating the stability or processing of SNORD44. This study reveals sRNA cell-compartment specific expression and the distinctive unique composition of the nucleolar sRNAs.
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