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Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality

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  • Evgenia Ntini, Denmark
  • Aino I Järvelin, Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg
  • ,
  • Jette Bornholdt, University of Copenhagen
  • ,
  • Yun Chen, Bioinformatics, Denmark
  • Mette Boyd, Institut for medicinsk biokemi og genetik, Afd. C, Denmark
  • Mette Jørgensen, University of Copenhagen
  • ,
  • Robin Andersson, Bioinformatics, Denmark
  • Ilka Hoof, Centre for Biological Sequence Analysis, Denmark
  • Aleks Schein
  • ,
  • Peter R Andersen
  • Pia K Andersen
  • Pascal Preker, Denmark
  • Eivind Valen, Bioinformatics, Denmark
  • Xiaobei Zhao, Bioinformatics, Denmark
  • Vicent Pelechano, Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg
  • ,
  • Lars M Steinmetz, Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg
  • ,
  • Albin Gustav Sandelin, Bioinformatics, Denmark
  • Torben Heick Jensen
Active human promoters produce promoter-upstream transcripts (PROMPTs). Why these RNAs are coupled to decay, whereas their neighboring promoter-downstream mRNAs are not, is unknown. Here high-throughput sequencing demonstrates that PROMPTs generally initiate in the antisense direction closely upstream of the transcription start sites (TSSs) of their associated genes. PROMPT TSSs share features with mRNA-producing TSSs, including stalled RNA polymerase II (RNAPII) and the production of small TSS-associated RNAs. Notably, motif analyses around PROMPT 3' ends reveal polyadenylation (pA)-like signals. Mutagenesis studies demonstrate that PROMPT pA signals are functional but linked to RNA degradation. Moreover, pA signals are under-represented in promoter-downstream versus promoter-upstream regions, thus allowing for more efficient RNAPII progress in the sense direction from gene promoters. We conclude that asymmetric sequence distribution around human gene promoters serves to provide a directional RNA output from an otherwise bidirectional transcription process.
Original languageEnglish
JournalNature Structural and Molecular Biology
Volume20
Issue8
Pages (from-to)923-928
Number of pages6
ISSN1545-9993
DOIs
Publication statusPublished - 14 Jul 2013

    Research areas

  • Base Sequence, Blotting, Northern, HeLa Cells, High-Throughput Nucleotide Sequencing, Humans, Molecular Sequence Data, Oligonucleotides, Polyadenylation, Promoter Regions, Genetic, RNA Polymerase II, RNA Stability, Transcription Initiation Site, Transcription, Genetic

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