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Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation

Different levels of regulatory mechanisms, including posttranscriptional regulation, are needed to elaborately regulate inflammatory responses to prevent harmful effects. Terminal uridyltransferase 7 (TUT7) controls RNA stability by adding uridines to its 3′ ends, but its function in innate immune r...

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Autores principales: Lin, Chia-Ching, Shen, Yi-Ru, Chang, Chi-Chih, Guo, Xiang-Yi, Young, Yun-Yun, Lai, Ting-Yu, Yu, I-Shing, Lee, Chih-Yuan, Chuang, Tsung-Hsien, Tsai, Hsin-Yue, Hsu, Li-Chung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241994/
https://www.ncbi.nlm.nih.gov/pubmed/34188032
http://dx.doi.org/10.1038/s41467-021-24177-7
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author Lin, Chia-Ching
Shen, Yi-Ru
Chang, Chi-Chih
Guo, Xiang-Yi
Young, Yun-Yun
Lai, Ting-Yu
Yu, I-Shing
Lee, Chih-Yuan
Chuang, Tsung-Hsien
Tsai, Hsin-Yue
Hsu, Li-Chung
author_facet Lin, Chia-Ching
Shen, Yi-Ru
Chang, Chi-Chih
Guo, Xiang-Yi
Young, Yun-Yun
Lai, Ting-Yu
Yu, I-Shing
Lee, Chih-Yuan
Chuang, Tsung-Hsien
Tsai, Hsin-Yue
Hsu, Li-Chung
author_sort Lin, Chia-Ching
collection PubMed
description Different levels of regulatory mechanisms, including posttranscriptional regulation, are needed to elaborately regulate inflammatory responses to prevent harmful effects. Terminal uridyltransferase 7 (TUT7) controls RNA stability by adding uridines to its 3′ ends, but its function in innate immune response remains obscure. Here we reveal that TLR4 activation induces TUT7, which in turn selectively regulates the production of a subset of cytokines, including Interleukin 6 (IL-6). TUT7 regulates IL-6 expression by controlling ribonuclease Regnase-1 mRNA (encoded by Zc3h12a gene) stability. Mechanistically, TLR4 activation causes TUT7 to bind directly to the stem-loop structure on Zc3h12a 3′-UTR, thereby promotes Zc3h12a uridylation and degradation. Zc3h12a from LPS-treated TUT7-sufficient macrophages possesses increased oligo-uridylated ends with shorter poly(A) tails, whereas oligo-uridylated Zc3h12a is significantly reduced in Tut7(-/-) cells after TLR4 activation. Together, our findings reveal the functional role of TUT7 in sculpting TLR4-driven responses by modulating mRNA stability of a selected set of inflammatory mediators.
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spelling pubmed-82419942021-07-20 Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation Lin, Chia-Ching Shen, Yi-Ru Chang, Chi-Chih Guo, Xiang-Yi Young, Yun-Yun Lai, Ting-Yu Yu, I-Shing Lee, Chih-Yuan Chuang, Tsung-Hsien Tsai, Hsin-Yue Hsu, Li-Chung Nat Commun Article Different levels of regulatory mechanisms, including posttranscriptional regulation, are needed to elaborately regulate inflammatory responses to prevent harmful effects. Terminal uridyltransferase 7 (TUT7) controls RNA stability by adding uridines to its 3′ ends, but its function in innate immune response remains obscure. Here we reveal that TLR4 activation induces TUT7, which in turn selectively regulates the production of a subset of cytokines, including Interleukin 6 (IL-6). TUT7 regulates IL-6 expression by controlling ribonuclease Regnase-1 mRNA (encoded by Zc3h12a gene) stability. Mechanistically, TLR4 activation causes TUT7 to bind directly to the stem-loop structure on Zc3h12a 3′-UTR, thereby promotes Zc3h12a uridylation and degradation. Zc3h12a from LPS-treated TUT7-sufficient macrophages possesses increased oligo-uridylated ends with shorter poly(A) tails, whereas oligo-uridylated Zc3h12a is significantly reduced in Tut7(-/-) cells after TLR4 activation. Together, our findings reveal the functional role of TUT7 in sculpting TLR4-driven responses by modulating mRNA stability of a selected set of inflammatory mediators. Nature Publishing Group UK 2021-06-29 /pmc/articles/PMC8241994/ /pubmed/34188032 http://dx.doi.org/10.1038/s41467-021-24177-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lin, Chia-Ching
Shen, Yi-Ru
Chang, Chi-Chih
Guo, Xiang-Yi
Young, Yun-Yun
Lai, Ting-Yu
Yu, I-Shing
Lee, Chih-Yuan
Chuang, Tsung-Hsien
Tsai, Hsin-Yue
Hsu, Li-Chung
Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation
title Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation
title_full Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation
title_fullStr Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation
title_full_unstemmed Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation
title_short Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation
title_sort terminal uridyltransferase 7 regulates tlr4-triggered inflammation by controlling regnase-1 mrna uridylation and degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241994/
https://www.ncbi.nlm.nih.gov/pubmed/34188032
http://dx.doi.org/10.1038/s41467-021-24177-7
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