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PMID: 19696892 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Genomic and transcriptional co-localization of protein-coding and long non-coding RNA pairs in the developing brain.

PLoS genetics ·Vol. 5 ·No. 8 ·2009-08-00 ·Pages e1000617

Ponjavic J, Oliver PL, Lunter G, Ponting CP

Abstract

Besides protein-coding mRNAs, eukaryotic transcriptomes include many long non-protein-coding RNAs (ncRNAs) of unknown function that are transcribed away from protein-coding loci. Here, we have identified 659 intergenic long ncRNAs whose genomic sequences individually exhibit evolutionary constraint, a hallmark of functionality. Of this set, those expressed in the brain are more frequently conserved and are significantly enriched with predicted RNA secondary structures. Furthermore, brain-expressed long ncRNAs are preferentially located adjacent to protein-coding genes that are (1) also expressed in the brain and (2) involved in transcriptional regulation or in nervous system development. This led us to the hypothesis that spatiotemporal co-expression of ncRNAs and nearby protein-coding genes represents a general phenomenon, a prediction that was confirmed subsequently by in situ hybridisation in developing and adult mouse brain. We provide the full set of constrained long ncRNAs as an important experimental resource and present, for the first time, substantive and predictive criteria for prioritising long ncRNA and mRNA transcript pairs when investigating their biological functions and contributions to development and disease.

MeSH Terms
Animals Biological Transport Brain/growth & development,metabolism Gene Expression Regulation, Developmental Genomics Mice Open Reading Frames RNA, Messenger/chemistry,genetics,metabolism RNA, Untranslated/chemistry,genetics,metabolism Transcription, Genetic
Chemicals
RNA, Messenger RNA, Untranslated
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ponjavic Jasmina
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Oliver Peter L
Lunter Gerton
Ponting Chris P
Conflict of Interest

The authors have declared that no competing interests exist.

References (58)
58 references, click to expand
  1. Ensembl 2006.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D556-61 PMID: 16381931
  2. The ZIC gene family in development and disease.
    Clin Genet. 2005 Apr;67(4):290-6 PMID: 15733262
  3. Genome-wide transcription and the implications for genomic organization.
    Nat Rev Genet. 2007 Jun;8(6):413-23 PMID: 17486121
  4. Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs.
    Genome Res. 2007 May;17(5):556-65 PMID: 17387145
  5. Global identification of human transcribed sequences with genome tiling arrays.
    Science. 2004 Dec 24;306(5705):2242-6 PMID: 15539566
  6. 3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA.
    Cell. 2008 Nov 28;135(5):919-32 PMID: 19041754
  7. Segmental duplications: organization and impact within the current human genome project assembly.
    Genome Res. 2001 Jun;11(6):1005-17 PMID: 11381028
  8. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription.
    Nature. 2008 Jul 3;454(7200):126-30 PMID: 18509338
  9. Evolution and functions of long noncoding RNAs.
    Cell. 2009 Feb 20;136(4):629-41 PMID: 19239885
  10. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator.
    Genes Dev. 2006 Jun 1;20(11):1470-84 PMID: 16705037
  11. Global variation in copy number in the human genome.
    Nature. 2006 Nov 23;444(7118):444-54 PMID: 17122850
  12. Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs.
    Nature. 2008 Nov 6;456(7218):130-4 PMID: 18820678
  13. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation.
    Genome Res. 2008 Sep;18(9):1433-45 PMID: 18562676
  14. Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF.
    J Med Genet. 2000 Jun;37(6):446-8 PMID: 10851256
  15. Hypertension in beta-adducin-deficient mice.
    Hypertension. 2000 Sep;36(3):449-53 PMID: 10988280
  16. 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
  17. Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates.
    Genome Res. 2007 May;17(5):545-55 PMID: 17387144
  18. Specific expression of long noncoding RNAs in the mouse brain.
    Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):716-21 PMID: 18184812
  19. 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
  20. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.
    Nature. 2002 Dec 5;420(6915):563-73 PMID: 12466851
  21. Genome-wide identification of human functional DNA using a neutral indel model.
    PLoS Comput Biol. 2006 Jan;2(1):e5 PMID: 16410828
  22. Genome-wide atlas of gene expression in the adult mouse brain.
    Nature. 2007 Jan 11;445(7124):168-76 PMID: 17151600
  23. RNA maps reveal new RNA classes and a possible function for pervasive transcription.
    Science. 2007 Jun 8;316(5830):1484-8 PMID: 17510325
  24. Highly conserved non-coding sequences are associated with vertebrate development.
    PLoS Biol. 2005 Jan;3(1):e7 PMID: 15630479
  25. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
    Genome Res. 2005 Aug;15(8):1034-50 PMID: 16024819
  26. GABAA receptors in central nervous system disease: anxiety, epilepsy, and insomnia.
    J Recept Signal Transduct Res. 2006;26(5-6):731-40 PMID: 17118808
  27. Aligning multiple genomic sequences with the threaded blockset aligner.
    Genome Res. 2004 Apr;14(4):708-15 PMID: 15060014
  28. Silencing by imprinted noncoding RNAs: is transcription the answer?
    Trends Genet. 2007 Jun;23(6):284-92 PMID: 17445943
  29. A gene atlas of the mouse and human protein-encoding transcriptomes.
    Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7 PMID: 15075390
  30. Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus.
    Mol Cell. 2000 Feb;5(2):377-86 PMID: 10882078
  31. Mammalian RNA polymerase II core promoters: insights from genome-wide studies.
    Nat Rev Genet. 2007 Jun;8(6):424-36 PMID: 17486122
  32. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
    Nat Genet. 2000 May;25(1):25-9 PMID: 10802651
  33. The transcriptional landscape of the mammalian genome.
    Science. 2005 Sep 2;309(5740):1559-63 PMID: 16141072
  34. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters.
    Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1412-7 PMID: 16432200
  35. Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism.
    Am J Hum Genet. 2005 Sep;77(3):377-88 PMID: 16080114
  36. The UCSC Genome Browser Database: 2008 update.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D773-9 PMID: 18086701
  37. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome.
    Genome Res. 2006 Jan;16(1):11-9 PMID: 16344565
  38. A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse.
    J Neurosci. 2003 Mar 1;23(5):1631-7 PMID: 12629167
  39. Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene.
    Nat Genet. 1994 Nov;8(3):251-5 PMID: 7874167
  40. Ripples from neighbouring transcription.
    Nat Cell Biol. 2008 Sep;10(9):1106-13 PMID: 19160492
  41. B2 RNA binds directly to RNA polymerase II to repress transcript synthesis.
    Nat Struct Mol Biol. 2004 Sep;11(9):822-9 PMID: 15300239
  42. The long and the short of RNA maps.
    Bioessays. 2007 Nov;29(11):1077-80 PMID: 17935150
  43. Genome-wide analysis of mammalian promoter architecture and evolution.
    Nat Genet. 2006 Jun;38(6):626-35 PMID: 16645617
  44. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes.
    Nature. 2001 Nov 15;414(6861):322-5 PMID: 11713533
  45. The role of chromatin structure in regulating the expression of clustered genes.
    Nat Rev Genet. 2005 Oct;6(10):775-81 PMID: 16160692
  46. Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia.
    Genome Res. 2003 Jun;13(6B):1273-89 PMID: 12819125
  47. Transcriptional interferences in cis natural antisense transcripts of humans and mice.
    Genetics. 2007 Jun;176(2):1299-306 PMID: 17409075
  48. Identification and classification of conserved RNA secondary structures in the human genome.
    PLoS Comput Biol. 2006 Apr;2(4):e33 PMID: 16628248
  49. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT.
    Science. 2005 Sep 2;309(5740):1570-3 PMID: 16141075
  50. Transcriptional and structural impact of TATA-initiation site spacing in mammalian core promoters.
    Genome Biol. 2006;7(8):R78 PMID: 16916456
  51. Sequence variants in SLITRK1 are associated with Tourette's syndrome.
    Science. 2005 Oct 14;310(5746):317-20 PMID: 16224024
  52. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription.
    Nature. 2001 Nov 15;414(6861):317-22 PMID: 11713532
  53. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution.
    Science. 2005 May 20;308(5725):1149-54 PMID: 15790807
  54. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
    Nature. 2009 Mar 12;458(7235):223-7 PMID: 19182780
  55. Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail.
    Nat Genet. 2001 Jul;28(3):251-5 PMID: 11431695
  56. The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock.
    Nat Struct Mol Biol. 2004 Sep;11(9):816-21 PMID: 15300240
  57. Brain-specific promoter and polyadenylation sites of the beta-adducin pre-mRNA generate an unusually long 3'-UTR.
    Nucleic Acids Res. 2006 Jan 09;34(1):243-53 PMID: 16414955
  58. Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes.
    BMC Genomics. 2004 Dec 21;5(1):99 PMID: 15613238
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000617
Published
2009-08-00
Epub
2009-00-21
Pages
e1000617
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2722021
Subset
IM
Grants
Medical Research Council · G0501331 · United Kingdom
Medical Research Council · MC_U137761446 · United Kingdom
External Links
PubMed source DOI: 10.1371/journal.pgen.1000617 PMC Full Text View journal details
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