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PMID: 22355166 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles.

RNA (New York, N.Y.) ·Vol. 18 ·No. 4 ·2012-04-00 ·Pages 738-51

Miyagawa R, Tano K, Mizuno R, Nakamura Y, Ijiri K, Rakwal R, Shibato J, Masuo Y, Mayeda A, Hirose T, Akimitsu N

Abstract

MALAT-1 noncoding RNA is localized to nuclear speckles despite its mRNA-like characteristics. Here, we report the identification of several key factors that promote the localization of MALAT-1 to nuclear speckles and also provide evidence that MALAT-1 is involved in the regulation of gene expression. Heterokaryon assays revealed that MALAT-1 does not shuttle between the nucleus and cytoplasm. RNAi-mediated repression of the nuclear speckle proteins, RNPS1, SRm160, or IBP160, which are well-known mRNA processing factors, resulted in the diffusion of MALAT-1 to the nucleoplasm. We demonstrated that MALAT-1 contains two distinct elements directing transcripts to nuclear speckles, which were also capable of binding to RNPS1 in vitro. Depletion of MALAT-1 represses the expression of several genes. Taken together, our results suggest that RNPS1, SRm160, and IBP160 contribute to the localization of MALAT-1 to nuclear speckles, where MALAT-1 could be involved in regulating gene expression.

MeSH Terms
Base Sequence Cell Nucleus/metabolism DNA Primers Down-Regulation HeLa Cells Humans RNA Interference RNA, Long Noncoding RNA, Untranslated/genetics,metabolism
Chemicals
DNA Primers MALAT1 long non-coding RNA, human RNA, Long Noncoding RNA, Untranslated
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Miyagawa Ryu
Radioisotope Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Tano Keiko
Mizuno Rie
Nakamura Yo
Ijiri Kenichi
Rakwal Randeep
Shibato Junko
Masuo Yoshinori
Mayeda Akila
Hirose Tetsuro
Akimitsu Nobuyoshi
References (67)
67 references, click to expand
  1. Pre-mRNA splicing: where and when in the nucleus.
    Trends Cell Biol. 2011 Jun;21(6):336-43 PMID: 21514162
  2. A spliceosomal intron binding protein, IBP160, links position-dependent assembly of intron-encoded box C/D snoRNP to pre-mRNA splicing.
    Mol Cell. 2006 Sep 1;23(5):673-84 PMID: 16949364
  3. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation.
    Mol Cell. 2008 Oct 24;32(2):232-46 PMID: 18951091
  4. The hnRNP C proteins contain a nuclear retention sequence that can override nuclear export signals.
    J Cell Biol. 1996 Sep;134(6):1365-73 PMID: 8830767
  5. Concepts in nuclear architecture.
    Bioessays. 2005 May;27(5):477-87 PMID: 15832379
  6. The nonsense-mediated decay RNA surveillance pathway.
    Annu Rev Biochem. 2007;76:51-74 PMID: 17352659
  7. A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway.
    Cell. 1995 Nov 3;83(3):415-22 PMID: 8521471
  8. Monitoring mRNA export.
    Curr Protoc Cell Biol. 2008 Dec;Chapter 22:Unit 22.13 PMID: 19085987
  9. The Air noncoding RNA: an imprinted cis-silencing transcript.
    Cold Spring Harb Symp Quant Biol. 2004;69:55-66 PMID: 16117633
  10. Introns play an essential role in splicing-dependent formation of the exon junction complex.
    Genes Dev. 2007 Aug 15;21(16):1993-8 PMID: 17675447
  11. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles.
    Mol Cell. 2009 Mar 27;33(6):717-26 PMID: 19217333
  12. Antiproliferative activity of the human IFN-alpha-inducible protein IFI44.
    J Interferon Cytokine Res. 2007 Aug;27(8):675-80 PMID: 17784819
  13. Molecular anatomy of a speckle.
    Anat Rec A Discov Mol Cell Evol Biol. 2006 Jul;288(7):664-75 PMID: 16761280
  14. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.
    Nature. 2007 Jun 14;447(7146):799-816 PMID: 17571346
  15. The SPINK gene family and celiac disease susceptibility.
    Immunogenetics. 2007 May;59(5):349-57 PMID: 17333166
  16. X chromosome dosage compensation: how mammals keep the balance.
    Annu Rev Genet. 2008;42:733-72 PMID: 18729722
  17. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs.
    Cell. 2011 Nov 11;147(4):773-88 PMID: 22078878
  18. Genome-wide transcription and the implications for genomic organization.
    Nat Rev Genet. 2007 Jun;8(6):413-23 PMID: 17486121
  19. MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles.
    Genome Res. 2009 Mar;19(3):347-59 PMID: 19106332
  20. Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm.
    Nature. 1992 Feb 20;355(6362):730-2 PMID: 1371331
  21. Proteomic analysis of interchromatin granule clusters.
    Mol Biol Cell. 2004 Aug;15(8):3876-90 PMID: 15169873
  22. Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU.
    Mol Cell. 2004 Jan 16;13(1):101-11 PMID: 14731398
  23. Compartmentalization of RNA processing factors within nuclear speckles.
    J Struct Biol. 2000 Apr;129(2-3):241-51 PMID: 10806074
  24. Genome-wide identification of polycomb-associated RNAs by RIP-seq.
    Mol Cell. 2010 Dec 22;40(6):939-53 PMID: 21172659
  25. Long non-coding RNAs: insights into functions.
    Nat Rev Genet. 2009 Mar;10(3):155-9 PMID: 19188922
  26. A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm.
    Genes Dev. 1998 Jan 1;12(1):55-66 PMID: 9420331
  27. The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons.
    J Cell Sci. 2007 Aug 1;120(Pt 15):2498-506 PMID: 17623775
  28. Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs.
    Nature. 2009 Feb 19;457(7232):1028-32 PMID: 19169241
  29. Nuclear domains.
    J Cell Sci. 2001 Aug;114(Pt 16):2891-3 PMID: 11686292
  30. Human RNPS1 and its associated factors: a versatile alternative pre-mRNA splicing regulator in vivo.
    Mol Cell Biol. 2004 Feb;24(3):1174-87 PMID: 14729963
  31. CENTROIDFOLD: a web server for RNA secondary structure prediction.
    Nucleic Acids Res. 2009 Jul;37(Web Server issue):W277-80 PMID: 19435882
  32. Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum.
    Genes Dev. 2007 Jan 1;21(1):11-42 PMID: 17210785
  33. Regulation of CD44 alternative splicing by SRm160 and its potential role in tumor cell invasion.
    Mol Cell Biol. 2006 Jan;26(1):362-70 PMID: 16354706
  34. Mammalian nuclei contain foci which are highly enriched in components of the pre-mRNA splicing machinery.
    EMBO J. 1991 Jan;10(1):195-206 PMID: 1824936
  35. Subnuclear organelles: new insights into form and function.
    Trends Cell Biol. 2006 Jan;16(1):19-26 PMID: 16325406
  36. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains.
    BMC Genomics. 2007 Feb 01;8:39 PMID: 17270048
  37. Exon junction complexes mediate the enhancing effect of splicing on mRNA expression.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11327-32 PMID: 12972633
  38. The expanding universe of noncoding RNAs.
    Cold Spring Harb Symp Quant Biol. 2006;71:551-64 PMID: 17381339
  39. Intranuclear distribution of poly(A) RNA determined by electron microscope in situ hybridization.
    Exp Cell Res. 1993 Sep;208(1):19-34 PMID: 7689476
  40. U1 and U2 small nuclear RNAs are present in nuclear speckles.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):305-8 PMID: 1530887
  41. Activation of pre-mRNA splicing by human RNPS1 is regulated by CK2 phosphorylation.
    Mol Cell Biol. 2005 Feb;25(4):1446-57 PMID: 15684395
  42. Nuclear speckles: a model for nuclear organelles.
    Nat Rev Mol Cell Biol. 2003 Aug;4(8):605-12 PMID: 12923522
  43. Discrete nuclear domains of poly(A) RNA and their relationship to the functional organization of the nucleus.
    J Cell Biol. 1991 Dec;115(5):1191-202 PMID: 1720123
  44. The RNA continent.
    Adv Cancer Res. 2008;99:77-112 PMID: 18037407
  45. Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts.
    Science. 2002 Oct 11;298(5592):419-22 PMID: 12228722
  46. Dosage compensation in mammals: fine-tuning the expression of the X chromosome.
    Genes Dev. 2006 Jul 15;20(14):1848-67 PMID: 16847345
  47. Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA.
    Mol Cell. 2009 Aug 28;35(4):467-78 PMID: 19716791
  48. Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA.
    Nature. 2011 May 15;474(7351):390-4 PMID: 21572438
  49. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation.
    Mol Cell. 2010 Sep 24;39(6):925-38 PMID: 20797886
  50. A mammalian gene with introns instead of exons generating stable RNA products.
    Nature. 1996 Feb 1;379(6564):464-6 PMID: 8559254
  51. Widespread transcription at neuronal activity-regulated enhancers.
    Nature. 2010 May 13;465(7295):182-7 PMID: 20393465
  52. The human 2'-5'oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation.
    Biochimie. 2007 Jun-Jul;89(6-7):779-88 PMID: 17408844
  53. Suggestive evidence for chromosomal localization of non-coding RNA from imprinted LIT1.
    J Hum Genet. 2007;52(11):926-933 PMID: 17917697
  54. An evolutionarily conserved role for SRm160 in 3'-end processing that functions independently of exon junction complex formation.
    J Biol Chem. 2003 Nov 7;278(45):44153-60 PMID: 12944400
  55. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
    Nature. 2009 Mar 12;458(7235):223-7 PMID: 19182780
  56. Divergent transcription from active promoters.
    Science. 2008 Dec 19;322(5909):1849-51 PMID: 19056940
  57. Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5'-terminal oligopyrimidine gene family reveals common features of snoRNA host genes.
    Mol Cell Biol. 1998 Dec;18(12):6897-909 PMID: 9819378
  58. Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes.
    Dev Biol. 1984 Feb;101(2):485-502 PMID: 6692991
  59. The assembly of a spliceosomal small nuclear ribonucleoprotein particle.
    Nucleic Acids Res. 2008 Nov;36(20):6482-93 PMID: 18854356
  60. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer.
    Oncogene. 2003 Sep 11;22(39):8031-41 PMID: 12970751
  61. Purification and characterization of human RNPS1: a general activator of pre-mRNA splicing.
    EMBO J. 1999 Aug 16;18(16):4560-70 PMID: 10449421
  62. MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles.
    Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2525-30 PMID: 19188602
  63. A coactivator of pre-mRNA splicing.
    Genes Dev. 1998 Apr 1;12(7):996-1009 PMID: 9531537
  64. New twists in X-chromosome inactivation.
    Curr Opin Cell Biol. 2008 Jun;20(3):349-55 PMID: 18508252
  65. The SRm160/300 splicing coactivator subunits.
    RNA. 2000 Jan;6(1):111-20 PMID: 10668804
  66. SR protein family members display diverse activities in the formation of nascent and mature mRNPs in vivo.
    Mol Cell. 2009 Apr 24;34(2):179-90 PMID: 19394295
  67. Structure and function in the nucleus.
    Science. 1998 Apr 24;280(5363):547-53 PMID: 9554838
Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1469-9001
Published
2012-04-00
Epub
2012-00-21
Pages
738-51
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC3312561
Subset
IM
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