期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 20, 期 8, 页码 923-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2640
关键词
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资金
- Danish National Research Foundation [DNRF58]
- Villum Kann Foundation
- Danish Cancer Society
- EU 7th Framework Programme (FP7/2007-2013)/European Research Council [204135]
- Novo Nordisk Foundation
- Lundbeck Foundation
- University of Luxembourg-Institute for Systems Biology Program
- Deutsche Forschungsgemeinschaft
- European Molecular Biology Organization postdoctoral grant
- Novo Nordisk Fonden [NNF12OC0001211] Funding Source: researchfish
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 (TSs) of their associated genes. PROM PT TSs share features with mRNA-producing TSs, including stalled RNA polymerase II (RNAPII) and the production of small TS-associated RNAs. Notably, motif analyses around PROM PT 3' ends reveal polyadenylation (pA)-like signals. Mutagenesis studies demonstrate that PROM PT 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.
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