MicroRNAs with a nucleolar location

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
RNA (Impact Factor: 4.94). 08/2009; 15(9):1705-15. DOI: 10.1261/rna.1470409
Source: PubMed


There is increasing evidence that noncoding RNAs play a functional role in the nucleus. We previously reported that the microRNA (miRNA), miR-206, is concentrated in the nucleolus of rat myoblasts, as well as in the cytoplasm as expected. Here we have extended this finding. We show by cell/nuclear fractionation followed by microarray analysis that a number of miRNAs can be detected within the nucleolus of rat myoblasts, some of which are significantly concentrated there. Pronounced nucleolar localization is a specific phenomenon since other miRNAs are present at only very low levels in the nucleolus and occur at much higher levels in the nucleoplasm and/or the cytoplasm. We have further characterized a subset of these miRNAs using RT-qPCR and in situ hybridization, and the results suggest that some miRNAs are present in the nucleolus in precursor form while others are present as mature species. Furthermore, we have found that these miRNAs are clustered in specific sites within the nucleolus that correspond to the classical granular component. One of these miRNAs is completely homologous to a portion of a snoRNA, suggesting that it may be processed from it. In contrast, the other nucleolar-concentrated miRNAs do not show homology with any annotated rat snoRNAs and thus appear to be present in the nucleolus for other reasons, such as modification/processing, or to play roles in the late stages of ribosome biosynthesis or in nonribosomal functions that have recently been ascribed to the granular component of the nucleolus.

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Available from: Joan Ritland
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    • "Nucleus cytoplasm Transcriptional regulation and alterantive splicing272829Rno-mir-206, Rno-mir-351, Rno-mir-494, Rno-mir-664, Rno-mir-1, Rno-let-7a, Rno-mir-21, Rno-mir-199a-3p, Rno-mir-125b-5p[30,31]Mmu-mir-709, Mmu-mir-805, Mmu-mir-690, Mmu-mir-122, Mmu-mir-30e[32]Hsa-mir-365, Hsa-mir-1, Hsa-mir-181c, Hsa-mir-720, let-7 familly, Hsa-mir-133a, Hsa-mir- 206, Hsa-mir-195, Hsa-mir-181a, Hsa-mir-181b "
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    ABSTRACT: More and more evidences suggested that the flow of genetic information can be spatially and temporally regulated by non-coding RNAs (ncRNAs), such as microRNAs (miRNAs). Although biogenesis and function of miRNAs have been well detailed, elucidation of the dynamic interplays between miRNAs and mRNAs have just begun. Here, we highlighted that the miRNA-mRNA interactions which could take place in different cellular locations. During dynamic interactions, miRNA binding sites included not only 3′UTRs, but also 5′UTRs and CDSs. Under different physiological or pathological conditions, miRNAs could switch from translational inhibition to activation. Dynamic miRNA-mRNA paradigms which suggested a novel tip of the iceberg beneath the gene regulation network will provide clues for function studies of other ncRNAs.
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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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