A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing

Akihiro Nita; Akinobu Matsumoto; Ronghao Tang; Chisa Shiraishi; Kazuya Ichihara; Daisuke Saito; Mikita Suyama; Tomoharu Yasuda; Gaku Tsuji; Masutaka Furue; Bumpei Katayama; Toshiyuki Ozawa; Teruasa Murata; Teruki Dainich; Kenji Kabashima; Atsushi Hatano; Masaki Matsumoto; Keiichi I. Nakayama

doi:10.1371/journal.pgen.1009686

A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing

Akihiro Nita, Akinobu Matsumoto, Ronghao Tang, Chisa Shiraishi, Kazuya Ichihara, Daisuke Saito, Mikita Suyama, Tomoharu Yasuda, Gaku Tsuji, Masutaka Furue, Bumpei Katayama, Toshiyuki Ozawa, Teruasa Murata, Teruki Dainich, Kenji Kabashima, Atsushi Hatano, Masaki Matsumoto, Keiichi I. Nakayama

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

10 Citations (Scopus)

Abstract

Although long noncoding RNAs (lncRNAs) are transcripts that do not encode proteins by definition, some lncRNAs actually contain small open reading frames that are translated. TINCR (terminal differentiation-induced ncRNA) has been recognized as a lncRNA that contributes to keratinocyte differentiation. However, we here show that TINCR encodes a ubiquitin-like protein that is well conserved among species and whose expression was confirmed by the generation of mice harboring a FLAG epitope tag sequence in the endogenous open reading frame as well as by targeted proteomics. Forced expression of this protein promoted cell cycle progression in normal human epidermal keratinocytes, and mice lacking this protein manifested a delay in skin wound healing associated with attenuated cell cycle progression in keratinocytes. We termed this protein TINCR-encoded ubiquitin-like protein (TUBL), and our results reveal a role for TINCR in the regulation of keratinocyte proliferation and skin regeneration that is dependent on TUBL.

Original language	English
Article number	e1009686
Journal	PLoS genetics
Volume	17
Issue number	8
DOIs	https://doi.org/10.1371/journal.pgen.1009686
Publication status	Published - Aug 5 2021

All Science Journal Classification (ASJC) codes

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Nita, A., Matsumoto, A., Tang, R., Shiraishi, C., Ichihara, K., Saito, D., Suyama, M., Yasuda, T., Tsuji, G., Furue, M., Katayama, B., Ozawa, T., Murata, T., Dainich, T., Kabashima, K., Hatano, A., Matsumoto, M., & Nakayama, K. I. (2021). A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing. PLoS genetics, 17(8), Article e1009686. https://doi.org/10.1371/journal.pgen.1009686

Nita, A, Matsumoto, A, Tang, R, Shiraishi, C, Ichihara, K, Saito, D , Suyama, M, Yasuda, T, Tsuji, G, Furue, M, Katayama, B, Ozawa, T, Murata, T, Dainich, T, Kabashima, K, Hatano, A, Matsumoto, M & Nakayama, KI 2021, 'A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing', PLoS genetics, vol. 17, no. 8, e1009686. https://doi.org/10.1371/journal.pgen.1009686

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title = "A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing",

abstract = "Although long noncoding RNAs (lncRNAs) are transcripts that do not encode proteins by definition, some lncRNAs actually contain small open reading frames that are translated. TINCR (terminal differentiation-induced ncRNA) has been recognized as a lncRNA that contributes to keratinocyte differentiation. However, we here show that TINCR encodes a ubiquitin-like protein that is well conserved among species and whose expression was confirmed by the generation of mice harboring a FLAG epitope tag sequence in the endogenous open reading frame as well as by targeted proteomics. Forced expression of this protein promoted cell cycle progression in normal human epidermal keratinocytes, and mice lacking this protein manifested a delay in skin wound healing associated with attenuated cell cycle progression in keratinocytes. We termed this protein TINCR-encoded ubiquitin-like protein (TUBL), and our results reveal a role for TINCR in the regulation of keratinocyte proliferation and skin regeneration that is dependent on TUBL.",

author = "Akihiro Nita and Akinobu Matsumoto and Ronghao Tang and Chisa Shiraishi and Kazuya Ichihara and Daisuke Saito and Mikita Suyama and Tomoharu Yasuda and Gaku Tsuji and Masutaka Furue and Bumpei Katayama and Toshiyuki Ozawa and Teruasa Murata and Teruki Dainich and Kenji Kabashima and Atsushi Hatano and Masaki Matsumoto and Nakayama, {Keiichi I.}",

note = "Funding Information: This work was supported in part by KAKENHI grants from Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science, and Technology of Japan (https://www.jsps.go.jp/ english/) to A.M. (20H05928) and to K.I.N. (18H05215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright: {\textcopyright} 2021 Nita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2021",

month = aug,

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doi = "10.1371/journal.pgen.1009686",

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T1 - A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing

AU - Nita, Akihiro

AU - Matsumoto, Akinobu

AU - Tang, Ronghao

AU - Shiraishi, Chisa

AU - Ichihara, Kazuya

AU - Saito, Daisuke

AU - Suyama, Mikita

AU - Yasuda, Tomoharu

AU - Tsuji, Gaku

AU - Furue, Masutaka

AU - Katayama, Bumpei

AU - Ozawa, Toshiyuki

AU - Murata, Teruasa

AU - Dainich, Teruki

AU - Kabashima, Kenji

AU - Hatano, Atsushi

AU - Matsumoto, Masaki

AU - Nakayama, Keiichi I.

N1 - Funding Information: This work was supported in part by KAKENHI grants from Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science, and Technology of Japan (https://www.jsps.go.jp/ english/) to A.M. (20H05928) and to K.I.N. (18H05215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright: © 2021 Nita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2021/8/5

Y1 - 2021/8/5

N2 - Although long noncoding RNAs (lncRNAs) are transcripts that do not encode proteins by definition, some lncRNAs actually contain small open reading frames that are translated. TINCR (terminal differentiation-induced ncRNA) has been recognized as a lncRNA that contributes to keratinocyte differentiation. However, we here show that TINCR encodes a ubiquitin-like protein that is well conserved among species and whose expression was confirmed by the generation of mice harboring a FLAG epitope tag sequence in the endogenous open reading frame as well as by targeted proteomics. Forced expression of this protein promoted cell cycle progression in normal human epidermal keratinocytes, and mice lacking this protein manifested a delay in skin wound healing associated with attenuated cell cycle progression in keratinocytes. We termed this protein TINCR-encoded ubiquitin-like protein (TUBL), and our results reveal a role for TINCR in the regulation of keratinocyte proliferation and skin regeneration that is dependent on TUBL.

AB - Although long noncoding RNAs (lncRNAs) are transcripts that do not encode proteins by definition, some lncRNAs actually contain small open reading frames that are translated. TINCR (terminal differentiation-induced ncRNA) has been recognized as a lncRNA that contributes to keratinocyte differentiation. However, we here show that TINCR encodes a ubiquitin-like protein that is well conserved among species and whose expression was confirmed by the generation of mice harboring a FLAG epitope tag sequence in the endogenous open reading frame as well as by targeted proteomics. Forced expression of this protein promoted cell cycle progression in normal human epidermal keratinocytes, and mice lacking this protein manifested a delay in skin wound healing associated with attenuated cell cycle progression in keratinocytes. We termed this protein TINCR-encoded ubiquitin-like protein (TUBL), and our results reveal a role for TINCR in the regulation of keratinocyte proliferation and skin regeneration that is dependent on TUBL.

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A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing

Abstract

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