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PMID: 19628621 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

MicroRNAs with a nucleolar location.

RNA (New York, N.Y.) ·Vol. 15 ·No. 9 ·2009-09-00 ·Pages 1705-15

Politz JC, Hogan EM, Pederson T

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.

MeSH Terms
Animals Cell Nucleolus/metabolism Cells, Cultured MicroRNAs/metabolism,physiology Microarray Analysis Myoblasts/metabolism Rats Tissue Distribution
Chemicals
MicroRNAs
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Politz Joan C Ritland
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. jritland@fhcrc.org
Hogan Eric M
Pederson Thoru
References (94)
94 references, click to expand
  1. Retrograde movement of tRNAs from the cytoplasm to the nucleus in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11290-5 PMID: 16040803
  2. The nucleolus: a site of ribonucleoprotein maturation.
    Curr Opin Cell Biol. 2003 Jun;15(3):318-25 PMID: 12787774
  3. Detection of myosin heavy chain mRNA during myogenesis in tissue culture by in vitro and in situ hybridization.
    Cell. 1977 Oct;12(2):501-8 PMID: 912755
  4. Human box H/ACA pseudouridylation guide RNA machinery.
    Mol Cell Biol. 2004 Jul;24(13):5797-807 PMID: 15199136
  5. New insights into nucleolar architecture and activity.
    Int Rev Cytol. 2006;255:177-235 PMID: 17178467
  6. Nucleolar localization of myc transcripts.
    Mol Cell Biol. 1993 Jun;13(6):3221-30 PMID: 7684491
  7. Nucleophosmin is a binding partner of nucleostemin in human osteosarcoma cells.
    Mol Biol Cell. 2008 Jul;19(7):2870-5 PMID: 18448670
  8. mRNA transport in yeast: time to reinvestigate the functions of the nucleolus.
    Mol Biol Cell. 1995 Apr;6(4):357-70 PMID: 7626803
  9. Three small nucleolar RNAs that are involved in ribosomal RNA precursor processing.
    Proc Natl Acad Sci U S A. 1997 May 13;94(10):4972-7 PMID: 9144174
  10. Extensive post-transcriptional regulation of microRNAs and its implications for cancer.
    Genes Dev. 2006 Aug 15;20(16):2202-7 PMID: 16882971
  11. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation.
    Genome Biol. 2004;5(3):R13 PMID: 15003116
  12. Ribosomal RNA synthesis and processing in a particulate site in the HeLa cell nucleus.
    Science. 1966 Nov 11;154(3750):786-9 PMID: 5919449
  13. Origins and Mechanisms of miRNAs and siRNAs.
    Cell. 2009 Feb 20;136(4):642-55 PMID: 19239886
  14. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts.
    Nature. 2008 Dec 18;456(7224):980-4 PMID: 19043405
  15. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs.
    Nat Rev Mol Cell Biol. 2007 Mar;8(3):209-20 PMID: 17318225
  16. miRNA and piRNA localization in the male mammalian meiotic nucleus.
    Chromosome Res. 2008;16(2):243-60 PMID: 18204908
  17. Nucleolar factors direct the 2'-O-ribose methylation and pseudouridylation of U6 spliceosomal RNA.
    Mol Cell Biol. 1999 Oct;19(10):6906-17 PMID: 10490628
  18. The structure of NoRC-associated RNA is crucial for targeting the chromatin remodelling complex NoRC to the nucleolus.
    EMBO Rep. 2008 Aug;9(8):774-80 PMID: 18600236
  19. Directed proteomic analysis of the human nucleolus.
    Curr Biol. 2002 Jan 8;12(1):1-11 PMID: 11790298
  20. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases.
    Nat Struct Mol Biol. 2006 Jan;13(1):13-21 PMID: 16369484
  21. miChip: an array-based method for microRNA expression profiling using locked nucleic acid capture probes.
    Nat Protoc. 2008;3(2):321-9 PMID: 18274534
  22. RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex.
    EMBO Rep. 2007 Aug;8(8):763-9 PMID: 17599088
  23. STUDIES ON ISOLATED NUCLEI. I. ISOLATION AND CHEMICAL CHARACTERIZATION OF A NUCLEAR FRACTION FROM GUINEA PIG LIVER.
    J Cell Biol. 1963 Aug;18:267-91 PMID: 14079489
  24. Organization of small nucleolar ribonucleoproteins (snoRNPs) by fluorescence in situ hybridization and immunocytochemistry.
    Mol Biol Cell. 1994 Dec;5(12):1289-99 PMID: 7535131
  25. Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma.
    Mod Pathol. 2009 Apr;22(4):547-55 PMID: 19287466
  26. Human ARF protein interacts with topoisomerase I and stimulates its activity.
    Oncogene. 2001 Feb 15;20(7):836-48 PMID: 11314011
  27. Primary microRNA transcripts are processed co-transcriptionally.
    Nat Struct Mol Biol. 2008 Sep;15(9):902-9 PMID: 19172742
  28. The multifunctional nucleolus.
    Nat Rev Mol Cell Biol. 2007 Jul;8(7):574-85 PMID: 17519961
  29. Fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy reveal the cytoplasmic origination of loaded nuclear RISC in vivo in human cells.
    Nucleic Acids Res. 2008 Nov;36(20):6439-49 PMID: 18842624
  30. RNA editing of a miRNA precursor.
    RNA. 2004 Aug;10(8):1174-7 PMID: 15272117
  31. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure.
    Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18255-60 PMID: 17108080
  32. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha.
    EMBO J. 2005 Jan 12;24(1):138-48 PMID: 15565168
  33. Biogenesis and intranuclear trafficking of human box C/D and H/ACA RNPs.
    Cold Spring Harb Symp Quant Biol. 2006;71:407-17 PMID: 17381323
  34. Building an efficient factory: where is pre-rRNA synthesized in the nucleolus?
    J Cell Biol. 2002 May 27;157(5):739-41 PMID: 12034767
  35. The nucleolus: the magician's hat for cell cycle tricks
    Curr Opin Cell Biol. 2000 Dec;12(6):752 PMID: 11063944
  36. MicroRNA-373 induces expression of genes with complementary promoter sequences.
    Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1608-13 PMID: 18227514
  37. MicroRNA-directed transcriptional gene silencing in mammalian cells.
    Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16230-5 PMID: 18852463
  38. Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing.
    RNA. 2008 Aug;14(8):1539-49 PMID: 18566191
  39. RNA editing of human microRNAs.
    Genome Biol. 2006;7(4):R27 PMID: 16594986
  40. microPrimer: the biogenesis and function of microRNA.
    Development. 2005 Nov;132(21):4645-52 PMID: 16224044
  41. A hexanucleotide element directs microRNA nuclear import.
    Science. 2007 Jan 5;315(5808):97-100 PMID: 17204650
  42. Distinctive patterns of microRNA expression in primary muscular disorders.
    Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17016-21 PMID: 17942673
  43. Specific requirements of MRFs for the expression of muscle specific microRNAs, miR-1, miR-206 and miR-133.
    Dev Biol. 2008 Sep 15;321(2):491-9 PMID: 18619954
  44. Intracellular localization and unique conserved sequences of three small nucleolar RNAs.
    Nucleic Acids Res. 1997 Apr 15;25(8):1591-6 PMID: 9092667
  45. Small silencing RNAs.
    Curr Biol. 2007 Sep 18;17(18):R789-93 PMID: 17878043
  46. An Argonaute transports siRNAs from the cytoplasm to the nucleus.
    Science. 2008 Jul 25;321(5888):537-41 PMID: 18653886
  47. Frequency and fate of microRNA editing in human brain.
    Nucleic Acids Res. 2008 Sep;36(16):5270-80 PMID: 18684997
  48. Aberrant mRNA transcripts and the nonsense-mediated decay proteins UPF2 and UPF3 are enriched in the Arabidopsis nucleolus.
    Plant Cell. 2009 Jul;21(7):2045-57 PMID: 19602621
  49. Dramatically improved RNA in situ hybridization signals using LNA-modified probes.
    RNA. 2005 Nov;11(11):1745-8 PMID: 16177135
  50. A novel noncoding RNA processed by Drosha is restricted to nucleus in mouse.
    RNA. 2008 Jul;14(7):1399-410 PMID: 18515546
  51. Single-cell c-myc gene expression in relationship to nuclear domains.
    Chromosome Res. 2008;16(2):325-43 PMID: 18320361
  52. General, rapid, and transcription-dependent fragmentation of nucleolar antigens in S. cerevisiae mRNA export mutants.
    RNA. 2008 Apr;14(4):706-16 PMID: 18258809
  53. MicroRNA-repressed mRNAs contain 40S but not 60S components.
    Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5343-8 PMID: 18390669
  54. Retrograde nuclear accumulation of cytoplasmic tRNA in rat hepatoma cells in response to amino acid deprivation.
    Proc Natl Acad Sci U S A. 2007 May 22;104(21):8845-50 PMID: 17502605
  55. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia.
    N Engl J Med. 2005 Oct 27;353(17):1793-801 PMID: 16251535
  56. Modulation of miRNA activity in human cancer: a new paradigm for cancer gene therapy?
    Cancer Gene Ther. 2008 Jun;15(6):341-55 PMID: 18369380
  57. miRNA editing--we should have inosine this coming.
    Mol Cell. 2007 Mar 23;25(6):792-3 PMID: 17386255
  58. Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10.
    Mol Cell Biol. 2000 Dec;20(23):9028-40 PMID: 11074001
  59. MicroRNA-206 colocalizes with ribosome-rich regions in both the nucleolus and cytoplasm of rat myogenic cells.
    Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18957-62 PMID: 17135348
  60. Primary microRNA transcript retention at sites of transcription leads to enhanced microRNA production.
    J Cell Biol. 2008 Jul 14;182(1):61-76 PMID: 18625843
  61. Real-time PCR quantification of precursor and mature microRNA.
    Methods. 2008 Jan;44(1):31-8 PMID: 18158130
  62. Identification of many microRNAs that copurify with polyribosomes in mammalian neurons.
    Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):360-5 PMID: 14691248
  63. Isolation and characterization of nuclei and purification of chromatin from differentiating cultures of rat skeletal muscle.
    Exp Cell Res. 1982 Jan;137(1):141-54 PMID: 7035194
  64. Signal recognition particle assembly in relation to the function of amplified nucleoli of Xenopus oocytes.
    J Cell Sci. 2005 Mar 15;118(Pt 6):1299-307 PMID: 15741230
  65. Nucleolar localization of DGCR8 and identification of eleven DGCR8-associated proteins.
    Exp Cell Res. 2007 Dec 10;313(20):4196-207 PMID: 17765891
  66. Real-time quantification of microRNAs by stem-loop RT-PCR.
    Nucleic Acids Res. 2005 Nov 27;33(20):e179 PMID: 16314309
  67. Post-transcriptional regulation of the let-7 microRNA during neural cell specification.
    FASEB J. 2007 Feb;21(2):415-26 PMID: 17167072
  68. A human snoRNA with microRNA-like functions.
    Mol Cell. 2008 Nov 21;32(4):519-28 PMID: 19026782
  69. Nonhistone chromosomal proteins in synchronized HeLa cells.
    Proc Natl Acad Sci U S A. 1972 Nov;69(11):3345-9 PMID: 4508327
  70. ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs.
    J Cell Biol. 2005 Jun 6;169(5):745-53 PMID: 15939761
  71. Muscle-specific microRNA miR-206 promotes muscle differentiation.
    J Cell Biol. 2006 Aug 28;174(5):677-87 PMID: 16923828
  72. Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing.
    Nucleic Acids Res. 2006;34(16):4622-9 PMID: 16963499
  73. Nucleostemin: a multiplex regulator of cell-cycle progression.
    Trends Cell Biol. 2008 Dec;18(12):575-9 PMID: 18951797
  74. Proteins associated with heterogeneous nuclear RNA in eukaryotic cells.
    J Mol Biol. 1974 Feb 25;83(2):163-83 PMID: 4821869
  75. snoRNA, a novel precursor of microRNA in Giardia lamblia.
    PLoS Pathog. 2008 Nov;4(11):e1000224 PMID: 19043559
  76. Mammalian mirtron genes.
    Mol Cell. 2007 Oct 26;28(2):328-36 PMID: 17964270
  77. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
    Nat Rev Genet. 2008 Feb;9(2):102-14 PMID: 18197166
  78. MicroRNAs flex their muscles.
    Trends Genet. 2008 Apr;24(4):159-66 PMID: 18325627
  79. A nonribosomal landscape in the nucleolus revealed by the stem cell protein nucleostemin.
    Mol Biol Cell. 2005 Jul;16(7):3401-10 PMID: 15857956
  80. In search of nonribosomal nucleolar protein function and regulation.
    J Cell Biol. 2009 Mar 23;184(6):771-6 PMID: 19289796
  81. Differences in vertebrate microRNA expression.
    Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14385-9 PMID: 16983084
  82. MicroRNA-206: the skeletal muscle-specific myomiR.
    Biochim Biophys Acta. 2008 Nov;1779(11):682-91 PMID: 18381085
  83. Signal recognition particle RNA localization within the nucleolus differs from the classical sites of ribosome synthesis.
    J Cell Biol. 2002 Nov 11;159(3):411-8 PMID: 12427865
  84. tRNA actively shuttles between the nucleus and cytosol in yeast.
    Science. 2005 Jul 1;309(5731):140-2 PMID: 15905365
  85. Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells.
    Mol Cell Biol. 1981 Dec;1(12):1138-49 PMID: 6180298
  86. Fibrillarin: a new protein of the nucleolus identified by autoimmune sera.
    Biol Cell. 1985;54(2):123-33 PMID: 2933102
  87. Signal recognition particle components in the nucleolus.
    Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):55-60 PMID: 10618370
  88. MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206.
    J Cell Biol. 2006 Oct 9;175(1):77-85 PMID: 17030984
  89. Small RNAs derived from snoRNAs.
    RNA. 2009 Jul;15(7):1233-40 PMID: 19474147
  90. Growth factors in the nucleolus?
    J Cell Biol. 1998 Oct 19;143(2):279-81 PMID: 9786941
  91. Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors.
    RNA. 2008 Jan;14(1):35-42 PMID: 18025253
  92. Localization of signal recognition particle RNA in the nucleolus of mammalian cells.
    Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7981-6 PMID: 9653126
  93. ADAR1 RNA deaminase limits short interfering RNA efficacy in mammalian cells.
    J Biol Chem. 2005 Feb 4;280(5):3946-53 PMID: 15556947
  94. Chromatin: its isolation from cultured mammalian cells with particular reference to contamination by nuclear ribnucleoprotein particles.
    Biochemistry. 1973 Jul 3;12(14):2766-73 PMID: 4736413
Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1469-9001
DOI
10.1261/rna.1470409
Email
jritland@fhcrc.org
Published
2009-09-00
Epub
2009-00-23
Pages
1705-15
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC2743059
Subset
IM
External Links
PubMed source DOI: 10.1261/rna.1470409 PMC Full Text View journal details
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