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PMID: 15317971 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification.

RNA (New York, N.Y.) ·Vol. 10 ·No. 9 ·2004-09-00 ·Pages 1309-22

Ohler U, Yekta S, Lim LP, Bartel DP, Burge CB

Abstract

MicroRNAs are approximately 22-nucleotide (nt) RNAs processed from foldback segments of endogenous transcripts. Some are known to play important gene regulatory roles during animal and plant development by pairing to the messages of protein-coding genes to direct the post-transcriptional repression of these messages. Previously, we developed a computational method called MiRscan, which scores features related to the foldbacks, and used this algorithm to identify new miRNA genes in the nematode Caenorhabditis elegans. In the present study, to identify sequences that might be involved in processing or transcriptional regulation of miRNAs, we aligned sequences upstream and downstream of orthologous nematode miRNA foldbacks. These alignments showed a pronounced peak in sequence conservation about 200 bp upstream of the miRNA foldback and revealed a highly significant sequence motif, with consensus CTCCGCCC, that is present upstream of almost all independently transcribed nematode miRNA genes. Scoring the pattern of upstream/downstream conservation, the occurrence of this sequence motif, and orthology of host genes for intronic miRNA candidates, yielded substantial improvements in the accuracy of MiRscan. Nine new C. elegans miRNA gene candidates were validated using a PCR-sequencing protocol. As previously seen for bacterial RNA genes, sequence features outside of the RNA secondary structure can therefore be very useful for the computational identification of eukaryotic noncoding RNA genes. The total number of confidently identified nematode miRNAs now approaches 100. The improved analysis supports our previous assertion that miRNA gene identification is nearing completion in C. elegans with apparently no more than 20 miRNA genes now remaining to be identified.

MeSH Terms
Animals Caenorhabditis elegans/genetics,growth & development Computational Biology/methods Conserved Sequence Evolution, Molecular Gene Expression Regulation Genes, Helminth MicroRNAs/chemistry,genetics,metabolism RNA Processing, Post-Transcriptional RNA, Helminth/chemistry,genetics RNA, Untranslated/chemistry,genetics,metabolism Transcription, Genetic
Chemicals
MicroRNAs RNA, Helminth RNA, Untranslated
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ohler Uwe
Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.
Yekta Soraya
Lim Lee P
Bartel David P
Burge Christopher B
References (56)
56 references, click to expand
  1. A uniform system for microRNA annotation.
    RNA. 2003 Mar;9(3):277-9 PMID: 12592000
  2. Identifying DNA and protein patterns with statistically significant alignments of multiple sequences.
    Bioinformatics. 1999 Jul-Aug;15(7-8):563-77 PMID: 10487864
  3. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila.
    Cell. 2003 Apr 4;113(1):25-36 PMID: 12679032
  4. The microRNAs of Caenorhabditis elegans.
    Genes Dev. 2003 Apr 15;17(8):991-1008 PMID: 12672692
  5. The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs.
    Dev Cell. 2003 May;4(5):625-37 PMID: 12737799
  6. The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target.
    Dev Cell. 2003 May;4(5):639-50 PMID: 12737800
  7. MicroRNAs and other tiny endogenous RNAs in C. elegans.
    Curr Biol. 2003 May 13;13(10):807-18 PMID: 12747828
  8. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.
    Nature. 2000 Feb 24;403(6772):901-6 PMID: 10706289
  9. A statistical method for finding transcription factor binding sites.
    Proc Int Conf Intell Syst Mol Biol. 2000;8:344-54 PMID: 10977095
  10. Identification and analysis of eukaryotic promoters: recent computational approaches.
    Trends Genet. 2001 Feb;17(2):56-60 PMID: 11173099
  11. Novel small RNA-encoding genes in the intergenic regions of Escherichia coli.
    Curr Biol. 2001 Jun 26;11(12):941-50 PMID: 11448770
  12. RNA-binding protein Nrd1 directs poly(A)-independent 3'-end formation of RNA polymerase II transcripts.
    Nature. 2001 Sep 20;413(6853):327-31 PMID: 11565036
  13. A computational analysis of sequence features involved in recognition of short introns.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11193-8 PMID: 11572975
  14. Identification of novel genes coding for small expressed RNAs.
    Science. 2001 Oct 26;294(5543):853-8 PMID: 11679670
  15. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):858-62 PMID: 11679671
  16. An extensive class of small RNAs in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):862-4 PMID: 11679672
  17. Non-coding RNA genes and the modern RNA world.
    Nat Rev Genet. 2001 Dec;2(12):919-29 PMID: 11733745
  18. Analysis of similarity within 142 pairs of orthologous intergenic regions of Caenorhabditis elegans and Caenorhabditis briggsae.
    Nucleic Acids Res. 2002 Mar 1;30(5):1233-9 PMID: 11861916
  19. Micro RNAs are complementary to 3' UTR sequence motifs that mediate negative post-transcriptional regulation.
    Nat Genet. 2002 Apr;30(4):363-4 PMID: 11896390
  20. An extensive network of coupling among gene expression machines.
    Nature. 2002 Apr 4;416(6880):499-506 PMID: 11932736
  21. Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells.
    Mol Cell. 2002 Jun;9(6):1327-33 PMID: 12086629
  22. MicroRNAs in plants.
    Genes Dev. 2002 Jul 1;16(13):1616-26 PMID: 12101121
  23. Endogenous and silencing-associated small RNAs in plants.
    Plant Cell. 2002 Jul;14(7):1605-19 PMID: 12119378
  24. Predictive identification of exonic splicing enhancers in human genes.
    Science. 2002 Aug 9;297(5583):1007-13 PMID: 12114529
  25. MicroRNA maturation: stepwise processing and subcellular localization.
    EMBO J. 2002 Sep 2;21(17):4663-70 PMID: 12198168
  26. CARPEL FACTORY, a Dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana.
    Curr Biol. 2002 Sep 3;12(17):1484-95 PMID: 12225663
  27. The expanding snoRNA world.
    Biochimie. 2002 Aug;84(8):775-90 PMID: 12457565
  28. Ensembl 2002: accommodating comparative genomics.
    Nucleic Acids Res. 2003 Jan 1;31(1):38-42 PMID: 12519943
  29. WormBase: a cross-species database for comparative genomics.
    Nucleic Acids Res. 2003 Jan 1;31(1):133-7 PMID: 12519966
  30. TRANSFAC: transcriptional regulation, from patterns to profiles.
    Nucleic Acids Res. 2003 Jan 1;31(1):374-8 PMID: 12520026
  31. Computational analysis of core promoters in the Drosophila genome.
    Genome Biol. 2002;3(12):RESEARCH0087 PMID: 12537576
  32. Sequence requirements for micro RNA processing and function in human cells.
    RNA. 2003 Jan;9(1):112-23 PMID: 12554881
  33. New microRNAs from mouse and human.
    RNA. 2003 Feb;9(2):175-9 PMID: 12554859
  34. Computational and experimental identification of C. elegans microRNAs.
    Mol Cell. 2003 May;11(5):1253-63 PMID: 12769849
  35. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing.
    Cell. 2003 Jun 13;113(6):673-6 PMID: 12809598
  36. Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity.
    Dev Biol. 2003 Jul 1;259(1):9-18 PMID: 12812784
  37. Computational identification of Drosophila microRNA genes.
    Genome Biol. 2003;4(7):R42 PMID: 12844358
  38. The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter.
    Dev Biol. 2003 Jul 15;259(2):364-79 PMID: 12871707
  39. The small RNA profile during Drosophila melanogaster development.
    Dev Cell. 2003 Aug;5(2):337-50 PMID: 12919683
  40. The nuclear RNase III Drosha initiates microRNA processing.
    Nature. 2003 Sep 25;425(6956):415-9 PMID: 14508493
  41. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans.
    Nature. 2003 Dec 18;426(6968):845-9 PMID: 14685240
  42. Prediction of mammalian microRNA targets.
    Cell. 2003 Dec 26;115(7):787-98 PMID: 14697198
  43. MicroRNAs modulate hematopoietic lineage differentiation.
    Science. 2004 Jan 2;303(5654):83-6 PMID: 14657504
  44. MicroRNAs: genomics, biogenesis, mechanism, and function.
    Cell. 2004 Jan 23;116(2):281-97 PMID: 14744438
  45. The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics.
    PLoS Biol. 2003 Nov;1(2):E45 PMID: 14624247
  46. MicroRNA-directed cleavage of HOXB8 mRNA.
    Science. 2004 Apr 23;304(5670):594-6 PMID: 15105502
  47. Comparative analysis of noncoding regions of 77 orthologous mouse and human gene pairs.
    Genome Res. 1999 Sep;9(9):815-24 PMID: 10508839
  48. Computational identification of plant microRNAs and their targets, including a stress-induced miRNA.
    Mol Cell. 2004 Jun 18;14(6):787-99 PMID: 15200956
  49. Tissue-specific expression of the human growth hormone gene is conferred in part by the binding of a specific trans-acting factor.
    EMBO J. 1987 Apr;6(4):971-81 PMID: 3595566
  50. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1.
    Cell. 1989 Dec 1;59(5):827-36 PMID: 2512012
  51. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
    Cell. 1993 Dec 3;75(5):843-54 PMID: 8252621
  52. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.
    Cell. 1993 Dec 3;75(5):855-62 PMID: 8252622
  53. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA.
    Cell. 1997 Mar 7;88(5):637-46 PMID: 9054503
  54. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  55. Bayesian adaptive sequence alignment algorithms.
    Bioinformatics. 1998;14(1):25-39 PMID: 9520499
  56. Vertebrate microRNA genes.
    Science. 2003 Mar 7;299(5612):1540 PMID: 12624257
Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1355-8382
DOI
10.1261/rna.5206304
Published
2004-09-00
Pages
1309-22
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC1370619
Subset
IM
External Links
PubMed source DOI: 10.1261/rna.5206304 PMC Full Text View journal details
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