Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Nat Struct Mol Biol. 2013 Aug;20(8):923-8. doi: 10.1038/nsmb.2640. Epub 2013 Jul 14.
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.
活跃的人类启动子产生启动子上游转录本（PROMPTs）。这些 RNA 为何与邻近的启动子下游 mRNA 不同，尚不清楚。本文通过高通量测序表明，PROMPTs 通常在其相关基因的转录起始位点（TSS）的反义方向上，在非常靠近 TSS 的上游起始。PROMPT TSS 与产生 mRNA 的 TSS 具有相同的特征，包括 RNA 聚合酶 II（RNAPII）停滞和小 TSS 相关 RNA 的产生。值得注意的是，PROMPT 3' 端附近的基序分析揭示了多聚腺苷酸化（pA）样信号。突变研究表明，PROMPT pA 信号是功能性的，但与 RNA 降解有关。此外，pA 信号在启动子下游与启动子上游区域的代表性不足，从而允许从基因启动子以顺式方向更有效地进行 RNAPII 前进。我们得出结论，不对称的序列分布围绕人类基因启动子，从双向转录过程中提供了定向的 RNA 输出。
