MicroRNAs with a nucleolar location

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
RNA (Impact Factor: 4.62). 08/2009; 15(9):1705-15. DOI: 10.1261/rna.1470409
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Joan Ritland, Jul 16, 2015
  • Source
    • "+ (Koberna et al. 2002) FC/DFC border FC, DFC, or FC/DFC border (Huang 2002) rRNA processing and ribosome subunits assembly + (Staněk et al. 2001) + (Beven et al. 1996) DFC and GC DFC and GC Viral infections + (Taliansky et al. 2011; Kim et al 2007) + (Dove et al. 2006; Emmott et al. 2008) DFC (Rakitina et al. 2011) DFC (Dove et al. 2006) HIV proteins/mRNA − + (Olson and Dundr 2005) DFC or GC Stress sensor and response Changes of morphology and composition (Stępiński 2009, 2010) + (Boulon et al. 2010) -p53 pathway − + (Olson 2004; Mayer and Grummt 2005; Suzuki et al. 2012; Krüger and Scheer 2010) nucleolar cavity (Krüger and Scheer 2010) -Without p53 pathway − + (Olausson et al. 2012) Regulation of tumor suppressor and oncogenic activity − + (Tsai and McKay 2002) Cell cycle regulation Yeast (Cockell and Gasser 1999; Visintin et al. 1999; Visintin and Amon 2000) Control of aging − + (Guarente 1997) Promotion of protein homeostasis via chaperones − + (Bański et al. 2010) Metabolism, modifications, assembly, or transport of RNAs and/or RNA-containing complexes + Brown and Shaw 2008; Shaw and Brown 2012 + (Brown and Shaw 2008; Shaw and Brown 2012) -mRNA + (Kim et al. 2009) + (Gururajan et al. 1994; Názer et al. 2012) -Signal recognition particles (SRP) RNA − + (Politz et al. 2000; Jacobson and Pederson 1998) -Small RNAs (snRNAs and snoRNAs) + (Kim et al. 2010) + (Gerbi et al. 2003) -tRNAs/RNase P proteins: Yeast (Bertrand et al. (1998) + (Jarrous et al. 1999) -Rpp14 and Rpp29 DFC -Rpp38 Allover nucleolus -Regulatory RNAs (siRNAs and miRNAs) + (Pontes et al. 2013) + (Politz et al. 2009) Nucleolar periphery and CBs -Modulation of telomerase function – + (Wang et al. 2010) Exon-junction complex (EJC) proteins in mRNA metabolism + (Brown and Shaw 2008; Pendle et al. 2005) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nucleoli are nuclear domains present in almost all eukaryotic cells. They not only specialize in the production of ribosomal subunits but also play roles in many fundamental cellular activities. Concerning ribosome biosynthesis, particular stages of this process, i.e., ribosomal DNA transcription, primary RNA transcript processing, and ribosome assembly proceed in precisely defined nucleolar subdomains. Although eukaryotic nucleoli are conservative in respect of their main function, clear morphological differences between these structures can be noticed between individual kingdoms. In most cases, a plant nucleolus shows well-ordered structure in which four main ultrastructural components can be distinguished: fibrillar centers, dense fibrillar component, granular component, and nucleolar vacuoles. Nucleolar chromatin is an additional crucial structural component of this organelle. Nucleolonema, although it is not always an unequivocally distinguished nucleolar domain, has often been described as a well-grounded morphological element, especially of plant nucleoli. The ratios and morphology of particular subcompartments of a nucleolus can change depending on its metabolic activity which in turn is correlated with the physiological state of a cell, cell type, cell cycle phase, as well as with environmental influence. Precise attribution of functions to particular nucleolar subregions in the process of ribosome biosynthesis is now possible using various approaches. The presented description of plant nucleolar morphology summarizes previous knowledge regarding the function of nucleoli as well as of their particular subdomains not only in the course of ribosome biosynthesis.
    Protoplasma 04/2014; 251(6). DOI:10.1007/s00709-014-0648-6 · 3.17 Impact Factor
  • Source
    • "Each miRNA may have as many as hundreds of mRNA targets [25] [26]. In general, miRNAs act in the cytoplasm, yet mature miRNAs has also been found in the nucleus [27] [28] [29] [30] [31] and nucleolus [32] [33] but the mechanisms of miRNAs subcellular localization and function are still not well understood [31] (Figure 1). miRNAs were originally found to play a role in the timing of larval development in Caenorhabditis elegans, which lead to the identification of lin-4 and let-7 miRNAs [18] [34]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Regulation of gene expression is essential for normal physiological functions; thus deregulation of gene expression is common in disease conditions. One level of regulation of gene expression is performed by noncoding RNAs, among which microRNAs (miRNA) are the best studied. Abnormal expression of these molecular players can lead to pathogenic processes such as heart disease, immune system abnormalities, and carcinogenesis, to name but a few. Of a length of 18–25 nucleotides miRNAs are involved in binding partial complementary sequences within the 3 í®í° -UTR (3 í®í° -untranslated region) of the target mRNAs. Depending on the type of neoplastic transformation, miRNAs can act both as oncogenes (oncomirs) or as tumor suppressors. Because of the great importance of miRNAs, most researches focus on either their role as biomarkers or their potential as therapeutic targets. Herein, we present the review of microRNA biology, function, and tumorigenic potential with emphasis on their role in lung cancer.
    Disease markers 01/2014; DOI:10.1155/2014/218169 · 2.17 Impact Factor
  • Source
    • "The canonical model of miRNA-mediated regulation indicates that miRNAs recognize their targets mostly in the cytoplasm after their nuclear exportation and maturation (Carthew and Sontheimer, 2009; Voinnet, 2009). However, current evidence uncovered the novel nucleus-localized expression patterns of mature miRNAs in both plants and animals (Politz et al., 2006, 2009; Wong et al., 2011). More specifically, in human beings, Hwang et al. (2007) discovered a hexanucleotide cis-element residing within miR-29b, which could direct nuclear import of the examined miRNAs and siRNAs. "
    Plant physiology 12/2011; 157(4):1583-95. DOI:10.1104/pp.111.187088 · 7.39 Impact Factor
Show more