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Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis
N(6)-methyladenosine (m(6)A) is the most abundant epigenetic modification in eukaryotic mRNAs and is essential for multiple RNA processing events during mammalian development and disease control. Here we show that conditional knockout of the m(6)A methyltransferase Mettl3 in bone marrow mesenchymal...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235890/ https://www.ncbi.nlm.nih.gov/pubmed/30429466 http://dx.doi.org/10.1038/s41467-018-06898-4 |
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author | Wu, Yunshu Xie, Liang Wang, Mengyuan Xiong, Qiuchan Guo, Yuchen Liang, Yu Li, Jing Sheng, Rui Deng, Peng Wang, Yuan Zheng, Rixin Jiang, Yizhou Ye, Ling Chen, Qianming Zhou, Xuedong Lin, Shuibin Yuan, Quan |
author_facet | Wu, Yunshu Xie, Liang Wang, Mengyuan Xiong, Qiuchan Guo, Yuchen Liang, Yu Li, Jing Sheng, Rui Deng, Peng Wang, Yuan Zheng, Rixin Jiang, Yizhou Ye, Ling Chen, Qianming Zhou, Xuedong Lin, Shuibin Yuan, Quan |
author_sort | Wu, Yunshu |
collection | PubMed |
description | N(6)-methyladenosine (m(6)A) is the most abundant epigenetic modification in eukaryotic mRNAs and is essential for multiple RNA processing events during mammalian development and disease control. Here we show that conditional knockout of the m(6)A methyltransferase Mettl3 in bone marrow mesenchymal stem cells (MSCs) induces pathological features of osteoporosis in mice. Mettl3 loss-of-function results in impaired bone formation, incompetent osteogenic differentiation potential and increased marrow adiposity. Moreover, Mettl3 overexpression in MSCs protects the mice from estrogen deficiency-induced osteoporosis. Mechanistically, we identify PTH (parathyroid hormone)/Pth1r (parathyroid hormone receptor-1) signaling axis as an important downstream pathway for m(6)A regulation in MSCs. Knockout of Mettl3 reduces the translation efficiency of MSCs lineage allocator Pth1r, and disrupts the PTH-induced osteogenic and adipogenic responses in vivo. Our results demonstrate the pathological outcomes of m(6)A mis-regulation in MSCs and unveil novel epitranscriptomic mechanism in skeletal health and diseases. |
format | Online Article Text |
id | pubmed-6235890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62358902018-11-16 Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis Wu, Yunshu Xie, Liang Wang, Mengyuan Xiong, Qiuchan Guo, Yuchen Liang, Yu Li, Jing Sheng, Rui Deng, Peng Wang, Yuan Zheng, Rixin Jiang, Yizhou Ye, Ling Chen, Qianming Zhou, Xuedong Lin, Shuibin Yuan, Quan Nat Commun Article N(6)-methyladenosine (m(6)A) is the most abundant epigenetic modification in eukaryotic mRNAs and is essential for multiple RNA processing events during mammalian development and disease control. Here we show that conditional knockout of the m(6)A methyltransferase Mettl3 in bone marrow mesenchymal stem cells (MSCs) induces pathological features of osteoporosis in mice. Mettl3 loss-of-function results in impaired bone formation, incompetent osteogenic differentiation potential and increased marrow adiposity. Moreover, Mettl3 overexpression in MSCs protects the mice from estrogen deficiency-induced osteoporosis. Mechanistically, we identify PTH (parathyroid hormone)/Pth1r (parathyroid hormone receptor-1) signaling axis as an important downstream pathway for m(6)A regulation in MSCs. Knockout of Mettl3 reduces the translation efficiency of MSCs lineage allocator Pth1r, and disrupts the PTH-induced osteogenic and adipogenic responses in vivo. Our results demonstrate the pathological outcomes of m(6)A mis-regulation in MSCs and unveil novel epitranscriptomic mechanism in skeletal health and diseases. Nature Publishing Group UK 2018-11-14 /pmc/articles/PMC6235890/ /pubmed/30429466 http://dx.doi.org/10.1038/s41467-018-06898-4 Text en © The Author(s) 2018 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/. |
spellingShingle | Article Wu, Yunshu Xie, Liang Wang, Mengyuan Xiong, Qiuchan Guo, Yuchen Liang, Yu Li, Jing Sheng, Rui Deng, Peng Wang, Yuan Zheng, Rixin Jiang, Yizhou Ye, Ling Chen, Qianming Zhou, Xuedong Lin, Shuibin Yuan, Quan Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis |
title | Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis |
title_full | Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis |
title_fullStr | Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis |
title_full_unstemmed | Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis |
title_short | Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis |
title_sort | mettl3-mediated m(6)a rna methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235890/ https://www.ncbi.nlm.nih.gov/pubmed/30429466 http://dx.doi.org/10.1038/s41467-018-06898-4 |
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