Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality

Evgenia Ntini, Aino I Järvelin, Jette Bornholdt, Yun Chen, Mette Boyd, Mette Jørgensen, Robin Andersson, Ilka Hoof, Aleks Schein, Peter R Andersen, Pia K Andersen, Pascal Preker, Eivind Valen, Xiaobei Zhao, Vicent Pelechano, Lars M Steinmetz, Albin Gustav Sandelin, Torben Heick Jensen

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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
Pages (from-to)923-928
Number of pages6
Publication statusPublished - 14 Jul 2013


  • 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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