Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction

Taisuke Kajino; Teppei Shimamura; Shuyi Gong; Kiyoshi Yanagisawa; Lisa Ida; Masahiro Nakatochi; Sebastian Griesing; Yukako Shimada; Keiko Kano; Motoshi Suzuki; Satoru Miyano; Takashi Takahashi

doi:10.15252/embj.201798441

Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction

Taisuke Kajino, Teppei Shimamura, Shuyi Gong, Kiyoshi Yanagisawa, Lisa Ida, Masahiro Nakatochi, Sebastian Griesing, Yukako Shimada, Keiko Kano, Motoshi Suzuki, Satoru Miyano, Takashi Takahashi

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Long non-coding RNAs (lncRNAs) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR-binding proteins identified PCBP2, while it was also found that MYMLR places a 557-kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes.

Original language	English
Article number	e98441
Journal	EMBO Journal
Volume	38
Issue number	17
DOIs	https://doi.org/10.15252/embj.201798441
Publication status	Published - 02-09-2019
Externally published	Yes

All Science Journal Classification (ASJC) codes

Neuroscience(all)
Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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title = "Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction",

abstract = "Long non-coding RNAs (lncRNAs) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR-binding proteins identified PCBP2, while it was also found that MYMLR places a 557-kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes.",

author = "Taisuke Kajino and Teppei Shimamura and Shuyi Gong and Kiyoshi Yanagisawa and Lisa Ida and Masahiro Nakatochi and Sebastian Griesing and Yukako Shimada and Keiko Kano and Motoshi Suzuki and Satoru Miyano and Takashi Takahashi",

note = "Funding Information: The authors thank Naoe Hotta for providing technical assistance and Ayumu Taguchi for helpful discussion during the process of revision. This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (15H05910), Grants-in-Aid for Scientific Research (A) (16H02468) and for Young Scientists (B) (16K19050) from the Japan Society for the Promotion of Science, a grant from the Princess Takamatsu Cancer Research Fund, and Japan Agency for Medical Research and development (AMED, 18ck0106363h0002). Publisher Copyright: {\textcopyright} 2019 The Authors",

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doi = "10.15252/embj.201798441",

language = "English",

volume = "38",

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T1 - Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction

AU - Kajino, Taisuke

AU - Shimamura, Teppei

AU - Gong, Shuyi

AU - Yanagisawa, Kiyoshi

AU - Ida, Lisa

AU - Nakatochi, Masahiro

AU - Griesing, Sebastian

AU - Shimada, Yukako

AU - Kano, Keiko

AU - Suzuki, Motoshi

AU - Miyano, Satoru

AU - Takahashi, Takashi

N1 - Funding Information: The authors thank Naoe Hotta for providing technical assistance and Ayumu Taguchi for helpful discussion during the process of revision. This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (15H05910), Grants-in-Aid for Scientific Research (A) (16H02468) and for Young Scientists (B) (16K19050) from the Japan Society for the Promotion of Science, a grant from the Princess Takamatsu Cancer Research Fund, and Japan Agency for Medical Research and development (AMED, 18ck0106363h0002). Publisher Copyright: © 2019 The Authors

PY - 2019/9/2

Y1 - 2019/9/2

N2 - Long non-coding RNAs (lncRNAs) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR-binding proteins identified PCBP2, while it was also found that MYMLR places a 557-kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes.

AB - Long non-coding RNAs (lncRNAs) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR-binding proteins identified PCBP2, while it was also found that MYMLR places a 557-kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes.

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Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction

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