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.
Original language | English |
---|---|
Journal | Nature Structural and Molecular Biology |
Volume | 20 |
Issue | 8 |
Pages (from-to) | 923-928 |
Number of pages | 6 |
ISSN | 1545-9993 |
DOIs | |
Publication status | Published - 14 Jul 2013 |
Keywords
- 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