TY - JOUR
T1 - Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals
AU - Uesaka, Masahiro
AU - Nishimura, Osamu
AU - Go, Yasuhiro
AU - Nakashima, Kinichi
AU - Agata, Kiyokazu
AU - Imamura, Takuya
N1 - Funding Information:
We thank the Great Ape Information Network (GAIN) and Kumamoto Sanctuary, Wildlife Research Center, Kyoto University for chimpanzee samples. We thank Atsushi Toyoda and Yutaka Suzuki for directional RNA sequencing, Takao Oishi and Hiroo Imai for primate sample preparation, Koichiro Irie and Hideyuki Nakashima for primary culture of murine cortical neuron, and Nobuhiko Hamazaki, Naoki Yamamoto, Naoyuki Fuse, Itoshi Nikaido, Hiroki Danno and Hiroki Ueda for useful discussions on directional RNA-seq analyses. We thank the National Institute of Genetics (NIG) and the Graduate School of Frontier Sciences in the University of Tokyo for technical assistance. We thank Elizabeth Nakajima for proofreading the manuscript. This work was supported in part by Grant-in-aid Nos. 21688021 and 24380158 (to T. I.), Global COE program A06 (to Kyoto University), the Grants to Excellent Graduate Schools (MEXT) program of Kyoto University, Grant-in-aid No. 221S0002 for Scientific Research on Innovative Areas “Genome Science” from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the Asahi Glass Foundation (to T. I.), and a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists (M.U.).
PY - 2014/1/17
Y1 - 2014/1/17
N2 - Background: 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.Results: 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.Conclusions: We propose that single-stranded ncRNA resulting from head-to-head transcription at GC-rich sequences regulates tissue-specific gene expression.
AB - Background: 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.Results: 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.Conclusions: 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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U2 - 10.1186/1471-2164-15-35
DO - 10.1186/1471-2164-15-35
M3 - Article
C2 - 24438357
AN - SCOPUS:84892465462
VL - 15
JO - BMC Genomics
JF - BMC Genomics
SN - 1471-2164
IS - 1
M1 - 35
ER -