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- Title
Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality.
- Authors
Ntini, Evgenia; Järvelin, Aino I; Bornholdt, Jette; Chen, Yun; Boyd, Mette; Jørgensen, Mette; Andersson, Robin; Hoof, Ilka; Schein, Aleks; Andersen, Peter R; Andersen, Pia K; Preker, Pascal; Valen, Eivind; Zhao, Xiaobei; Pelechano, Vicent; Steinmetz, Lars M; Sandelin, Albin; Jensen, Torben Heick
- Abstract
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.
- Subjects
HUMAN genome; PROMOTERS (Genetics); NUCLEOTIDE sequence; ANTISENSE DNA; ADENYLATION (Biochemistry)
- Publication
Nature Structural & Molecular Biology, 2013, Vol 20, Issue 8, p923
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2640