NAIL: An evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis

Aklncllar, Semih Can; Wu, Lele; Ng, Qin Feng; Chua, Joelle Yi Heng; Unal, Bilal; Noda, Taichi; Chor, Wei Hong Jeff; Ikawa, Masahito; Tergaonkar, Vinay

doi:https://doi.org/10.1136/gutjnl-2020-322980

NAIL: An evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis

Aklncllar, Semih Can; Wu, Lele; Ng, Qin Feng et al.

Gut, 2020, 70(10), 1857-1871

アクセス数:252件（2025-04-18 02:58 集計）

固定URL: https://hdl.handle.net/11094/78550

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タイトル	NAIL: An evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis
著者	著者名 Aklncllar, Semih Can
	著者名 Wu, Lele
	著者名 Ng, Qin Feng
	著者名 Chua, Joelle Yi Heng
	著者名 Unal, Bilal
	NRID 1000050712551 1000050712551 著者名 Noda, Taichi
	著者名 Chor, Wei Hong Jeff
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 著者名 Ikawa, Masahito
	著者名 Tergaonkar, Vinay
キーワード等	chronic ulcerative colitis
	inflammation
	inflammatory bowel disease
内容	Akıncılar SC, Wu L, NG QF, et al., NAIL: an evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis. Gut Published Online First: 25 November 2020. doi: 10.1136/gutjnl-2020-322980
抄録	Objective: NFκB is the key modulator in inflammatory disorders. However, the key regulators that activate, fine-tune or shut off NFκB activity in inflammatory conditions are poorly understood. In this study, we aim to investigate the roles that NFκB-specific long non-coding RNAs (lncRNAs) play in regulating inflammatory networks. Design: Using the first genetic-screen to identify NFκB-specific lncRNAs, we performed RNA-seq from the p65-/- and Ikkβ-/- mouse embryonic fibroblasts and report the identification of an evolutionary conserved lncRNA designated mNAIL (mice) or hNAIL (human). hNAIL is upregulated in human inflammatory disorders, including UC. We generated mNAILÎ "NFκB mice, wherein deletion of two NFκB sites in the proximal promoter of mNAIL abolishes its induction, to study its function in colitis. Results: NAIL regulates inflammation via sequestering and inactivating Wip1, a known negative regulator of proinflammatory p38 kinase and NFκB subunit p65. Wip1 inactivation leads to coordinated activation of p38 and covalent modifications of NFκB, essential for its genome-wide occupancy on specific targets. NAIL enables an orchestrated response for p38 and NFκB coactivation that leads to differentiation of precursor cells into immature myeloid cells in bone marrow, recruitment of macrophages to inflamed area and expression of inflammatory genes in colitis. Conclusion: NAIL directly regulates initiation and progression of colitis and its expression is highly correlated with NFκB activity which makes it a perfect candidate to serve as a biomarker and a therapeutic target for IBD and other inflammation-associated diseases.
出版者	BMJ Publishing Group
収録物名	Gut
巻(号)	70(10)
ページ	1857-1871
刊行年月	2020
言語	英語
ハンドルURL	https://hdl.handle.net/11094/78550
PISSN	00175749
eISSN	14683288
NCID	AA12306353
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1136/gutjnl-2020-322980
アクセス権	open access
権利情報	© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Gut. 2020, 70(10), p. 1857-1871
DC.title	NAIL: An evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis
DC.creator	Aklncllar, Semih Can
	Wu, Lele
	Ng, Qin Feng
	Chua, Joelle Yi Heng
	Unal, Bilal
	Noda, Taichi
	Chor, Wei Hong Jeff
	Ikawa, Masahito
	Tergaonkar, Vinay
DC.publisher	BMJ Publishing Group
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020
DC.identifier	https://doi.org/10.1136/gutjnl-2020-322980
DC.subject	chronic ulcerative colitis
	inflammation
	inflammatory bowel disease
DC.description	Akıncılar SC, Wu L, NG QF, et al., NAIL: an evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis. Gut Published Online First: 25 November 2020. doi: 10.1136/gutjnl-2020-322980
DCTERMS.abstract	Objective: NFκB is the key modulator in inflammatory disorders. However, the key regulators that activate, fine-tune or shut off NFκB activity in inflammatory conditions are poorly understood. In this study, we aim to investigate the roles that NFκB-specific long non-coding RNAs (lncRNAs) play in regulating inflammatory networks. Design: Using the first genetic-screen to identify NFκB-specific lncRNAs, we performed RNA-seq from the p65-/- and Ikkβ-/- mouse embryonic fibroblasts and report the identification of an evolutionary conserved lncRNA designated mNAIL (mice) or hNAIL (human). hNAIL is upregulated in human inflammatory disorders, including UC. We generated mNAILÎ "NFκB mice, wherein deletion of two NFκB sites in the proximal promoter of mNAIL abolishes its induction, to study its function in colitis. Results: NAIL regulates inflammation via sequestering and inactivating Wip1, a known negative regulator of proinflammatory p38 kinase and NFκB subunit p65. Wip1 inactivation leads to coordinated activation of p38 and covalent modifications of NFκB, essential for its genome-wide occupancy on specific targets. NAIL enables an orchestrated response for p38 and NFκB coactivation that leads to differentiation of precursor cells into immature myeloid cells in bone marrow, recruitment of macrophages to inflamed area and expression of inflammatory genes in colitis. Conclusion: NAIL directly regulates initiation and progression of colitis and its expression is highly correlated with NFκB activity which makes it a perfect candidate to serve as a biomarker and a therapeutic target for IBD and other inflammation-associated diseases.
DC.rights	© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	78550
citation_title	NAIL: An evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis
citation_author	Aklncllar, Semih Can
	Wu, Lele
	Ng, Qin Feng
	Chua, Joelle Yi Heng
	Unal, Bilal
	Noda, Taichi
	Chor, Wei Hong Jeff
	Ikawa, Masahito
	Tergaonkar, Vinay
citation_publisher	BMJ Publishing Group
citation_language	英語
citation_date	2020
citation_journal_title	Gut
citation_volume	70
citation_issue	10
citation_firstpage	1857
citation_lastpage	1871
citation_doi	https://doi.org/10.1136/gutjnl-2020-322980
citation_public_url	https://hdl.handle.net/11094/78550

NAIL: An evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis

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