Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Nucleic Acids Res. 2012 Mar;40(6):2432-44. doi: 10.1093/nar/gkr1121. Epub 2011 Nov 28.
The precise nature of antisense transcripts in eukaryotes such as Saccharomyces cerevisiae remains elusive. Here we show that the 3' regions of genes possess a promoter architecture, including a pre-initiation complex (PIC), which mirrors that at the 5' region and which is much more pronounced at genes with a defined antisense transcript. Remarkably, for genes with an antisense transcript, average levels of PIC components at the 3' region are ∼60% of those at the 5' region. Moreover, at these genes, average levels of nascent antisense transcription are ∼45% of sense transcription. We find that this 3' promoter architecture persists for highly transcribed antisense transcripts where there are only low levels of transcription in the divergent sense direction, suggesting that the 3' regions of genes can drive antisense transcription independent of divergent sense transcription. To validate this, we insert short 3' regions into the middle of other genes and find that they are capable of both initiating antisense transcripts and terminating sense transcripts. Our results suggest that antisense transcription can be regulated independently of divergent sense transcription in a PIC-dependent manner and we propose that regulated production of antisense transcripts represents a fundamental and widespread component of gene regulation.
真核生物（如酿酒酵母）中反义转录本的确切性质仍然难以捉摸。在这里，我们表明基因的 3' 区域具有启动子结构，包括起始前复合物（PIC），其与 5' 区域的启动子结构相似，并且在具有明确反义转录本的基因中更为明显。值得注意的是，对于具有反义转录本的基因，3' 区域的 PIC 成分的平均水平约为 5' 区域的 60%。此外，在这些基因中，新生反义转录的平均水平约为有义转录的 45%。我们发现，这种 3' 启动子结构在高度转录的反义转录本中仍然存在，其中在发散的有义方向上仅有低水平的转录，这表明基因的 3' 区域可以独立于发散的有义转录来驱动反义转录。为了验证这一点，我们将短的 3' 区域插入到其他基因的中间，发现它们能够启动反义转录本并终止有义转录本。我们的结果表明，反义转录可以以 PIC 依赖性的方式独立于发散的有义转录进行调节，我们提出反义转录本的调控产生代表基因调控的一个基本和广泛的组成部分。
