Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals.

Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals.
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DOI:
10.1186/1471-2164-15-35
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发表时间:
2014-01-17
期刊:
影响因子:
4.4
通讯作者:
Imamura T
Imamura T
中科院分区:
生物学2区
文献类型:
--
作者:
Uesaka M;Nishimura O;Go Y;Nakashima K;Agata K;Imamura T

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大多数参与哺乳动物mRNA代谢的非编码RNA(ncRNA)被认为通过形成短或长的ncRNA-mRNA双链体结构,以转录前或转录后的方式下调相应的mRNA表达水平。有关非双链体长 ncRNA 的信息现在也在迅速积累。为了在全基因组水平上检查转录的定向特性,我们对小鼠和黑猩猩组织样本进行了定向 RNA-seq 分析。我们发现只有大约 1% 的基因组中顶部链和底部链都用于转录,这表明 RNA-RNA 双链体的形成并不丰富。对蛋白质编码基因的转录起始位点(TSS)的关注表明,其中很大一部分含有区分反义和有义偏向转录的转换点,这表明头对头转录比之前认为的更为普遍。 90%以上的头对头型启动子含有CpG岛。此外,CCG 和 CGG 重复序列分别在位于头对头型启动子中的 TSS 的上游区域和下游区域显着富集。具有组织特异性启动子相关ncRNA(pancRNA)的基因显示其pancRNA和mRNA的表达之间呈正相关,这与pancRNA在兼性基因激活中的作用一致,而具有组成型表达的基因通常缺乏pancRNA。我们提出,在富含 GC 的序列上头对头转录产生的单链 ncRNA 调节组织特异性基因表达。
The majority of non-coding RNAs (ncRNAs) involved in mRNA metabolism in mammals have been believed to downregulate the corresponding mRNA expression level in a pre- or post-transcriptional manner by forming short or long ncRNA-mRNA duplex structures. Information on non-duplex-forming long ncRNAs is now also rapidly accumulating. To examine the directional properties of transcription at the whole-genome level, we performed directional RNA-seq analysis of mouse and chimpanzee tissue samples. We found that there is only about 1% of the genome where both the top and bottom strands are utilized for transcription, suggesting that RNA-RNA duplexes are not abundantly formed. Focusing on transcription start sites (TSSs) of protein-coding genes revealed that a significant fraction of them contain switching-points that separate antisense- and sense-biased transcription, suggesting that head-to-head transcription is more prevalent than previously thought. 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. Genes with tissue-specific promoter-associated ncRNAs (pancRNAs) show a positive correlation between the expression of their pancRNA and mRNA, which is in accord with the proposed role of pancRNA in facultative gene activation, whereas genes with constitutive expression generally lack pancRNAs. We propose that single-stranded ncRNA resulting from head-to-head transcription at GC-rich sequences regulates tissue-specific gene expression.
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