Abundant Bidirectional Transcription around Transcription Start Sites in Mammals

In mammals, more than 60% of the genome is use for transcription for mRNAs and noncoding RNAs (ncRNAs). A fraction of ncRNAs have been believed to downregulate the corresponding mRNA expression level in a pre- or post- transcriptional manner by forming RNA-RNA duplex structures.To examine the directional properties of transcription at the whole genome level, we performed directional RNA-seq analysis of mouse brain and heart samples. Our analysis revealed that there is only a small fraction of the genome where both the top and bottom strands are utilized for transcription.A significant fraction of transcription start sites (TSSs) of protein-coding genes contain borders that separate antisense- and sense-biased transcription, suggesting that head-to-head transcription at the TSS is more prevalent than previously thought.The expression of the resultant promoter-associated ncRNAs (pancRNAs) tends to occur together with that of the corresponding mRNA in a coordinated manner. A fraction of genes with tissue-specific pancRNAs show a positive correlation between their pancRNA and mRNA expression, which is in accord with the proposed role for pancRNA in facultative gene activation, whereas genes with constitutive expression lack an association with pancRNA. More than 90% of head-to-head type promoters contain CpG islands. Moreover, CCG and CGG repeats are significantly enriched in the upstream regions and downstream regions, respectively, of TSSs located in head-to-head type promoters. Here, we propose that head-to-head transcription from GC-rich sequences regulates gene expression.

在哺乳动物中，超过60%的基因组会被用于信使RNA（mRNA）和非编码RNA（ncRNA）的转录。此前学界认为，一部分非编码RNA可通过形成RNA-RNA双链结构，以转录前或转录后方式下调对应信使RNA的表达水平。为探究全基因组水平的转录方向特性，我们对小鼠大脑与心脏样本开展了定向RNA测序分析。分析结果显示，仅有极少部分基因组的正、负链均被用于转录。大量蛋白编码基因的转录起始位点（TSS）存在分隔反义偏好与正义偏好转录的边界，这表明转录起始位点处的头对头转录现象比此前认知更为普遍。由此产生的启动子相关非编码RNA（pancRNAs）的表达，往往与对应信使RNA的表达呈现协同模式。一部分携带组织特异性pancRNA的基因，其pancRNA与mRNA的表达呈正相关，这与pancRNA在兼性基因激活中所扮演的已被提出的功能相符；而组成型表达的基因则与pancRNA无关联。超过90%的头对头型启动子含有CpG岛。此外，位于头对头型启动子的转录起始位点，其上游区域与下游区域分别显著富集CCG与CGG重复序列。据此我们提出：源自GC富集序列的头对头转录可调控基因表达。