title: Transcription factor binding sites are highly enriched within microRNA precursor sequences.
abstract: BACKGROUND
  Transcription factors are thought to regulate the transcription of microRNA genes in a manner similar to that of protein-coding genes; that is, by binding to conventional transcription factor binding site DNA sequences located in or near promoter regions that lie upstream of the microRNA genes. However, in the course of analyzing the genomics of human microRNA genes, we noticed that annotated transcription factor binding sites commonly lie within 70- to 110-nt long microRNA small hairpin precursor sequences.
  
  
  RESULTS
  We report that about 45% of all human small hairpin microRNA (pre-miR) sequences contain at least one predicted transcription factor binding site motif that is conserved across human, mouse and rat, and this rises to over 75% if one excludes primate-specific pre-miRs. The association is robust and has extremely strong statistical significance; it affects both intergenic and intronic pre-miRs and both isolated and clustered microRNA genes. We also confirmed and extended this finding using a separate analysis that examined all human pre-miR sequences regardless of conservation across species.
  
  
  CONCLUSIONS
  The transcription factor binding sites localized within small hairpin microRNA precursor sequences may possibly regulate their transcription. Transcription factors may also possibly bind directly to nascent primary microRNA gene transcripts or small hairpin microRNA precursors and regulate their processing.
authors.affiliation: Genome Institute, National Center for Genetic Engineering and Biotechnology, Klong1, Klong Luang, Pathumthani 12120, Thailand.
authors.forename: Jittima
authors.initials: J
authors.lastname: Piriyapongsa
authors.forename: I King
authors.initials: IK
authors.lastname: Jordan
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Conley
authors.forename: Tom
authors.initials: T
authors.lastname: Ronan
authors.forename: Neil R
authors.initials: NR
authors.lastname: Smalheiser
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology; D017124:Conserved Sequence; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors