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A local translation program regulates centriole amplification in the airway epithelium
Biogenesis of organelles requires targeting of a subset of proteins to specific subcellular domains by signal peptides or mechanisms controlling mRNA localization and local translation. How local distribution and translation of specific mRNAs for organelle biogenesis is achieved remains elusive and...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151349/ https://www.ncbi.nlm.nih.gov/pubmed/37127654 http://dx.doi.org/10.1038/s41598-023-34365-8 |
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author | Liu, Helu Li, Huijun Jiang, Zhihua Jin, Shibo Song, Rui Yang, Ying Li, Jun Huang, Jingshu Zhang, Xiaoqing Dong, Xuesong Mori, Munemasa Fritzler, Marvin J. He, Lin Cardoso, Wellington V. Lu, Jining |
author_facet | Liu, Helu Li, Huijun Jiang, Zhihua Jin, Shibo Song, Rui Yang, Ying Li, Jun Huang, Jingshu Zhang, Xiaoqing Dong, Xuesong Mori, Munemasa Fritzler, Marvin J. He, Lin Cardoso, Wellington V. Lu, Jining |
author_sort | Liu, Helu |
collection | PubMed |
description | Biogenesis of organelles requires targeting of a subset of proteins to specific subcellular domains by signal peptides or mechanisms controlling mRNA localization and local translation. How local distribution and translation of specific mRNAs for organelle biogenesis is achieved remains elusive and likely to be dependent on the cellular context. Here we identify Trinucleotide repeat containing-6a (Tnrc6a), a component of the miRNA pathway, distinctively localized to apical granules of differentiating airway multiciliated cells (MCCs) adjacent to centrioles. In spite of being enriched in TNRC6A and the miRNA-binding protein AGO2, they lack enzymes for mRNA degradation. Instead, we found these apical granules enriched in components of the mRNA translation machinery and newly synthesized proteins suggesting that they are specific hubs for target mRNA localization and local translation in MCCs. Consistent with this, Tnrc6a loss of function prevented formation of these granules and led to a broad reduction, rather than stabilization of miRNA targets. These included downregulation of key genes involved in ciliogenesis and was associated with defective multicilia formation both in vivo and in primary airway epithelial cultures. Similar analysis of Tnrc6a disruption in yolk sac showed stabilization of miRNA targets, highlighting the potential diversity of these mechanisms across organs. |
format | Online Article Text |
id | pubmed-10151349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101513492023-05-03 A local translation program regulates centriole amplification in the airway epithelium Liu, Helu Li, Huijun Jiang, Zhihua Jin, Shibo Song, Rui Yang, Ying Li, Jun Huang, Jingshu Zhang, Xiaoqing Dong, Xuesong Mori, Munemasa Fritzler, Marvin J. He, Lin Cardoso, Wellington V. Lu, Jining Sci Rep Article Biogenesis of organelles requires targeting of a subset of proteins to specific subcellular domains by signal peptides or mechanisms controlling mRNA localization and local translation. How local distribution and translation of specific mRNAs for organelle biogenesis is achieved remains elusive and likely to be dependent on the cellular context. Here we identify Trinucleotide repeat containing-6a (Tnrc6a), a component of the miRNA pathway, distinctively localized to apical granules of differentiating airway multiciliated cells (MCCs) adjacent to centrioles. In spite of being enriched in TNRC6A and the miRNA-binding protein AGO2, they lack enzymes for mRNA degradation. Instead, we found these apical granules enriched in components of the mRNA translation machinery and newly synthesized proteins suggesting that they are specific hubs for target mRNA localization and local translation in MCCs. Consistent with this, Tnrc6a loss of function prevented formation of these granules and led to a broad reduction, rather than stabilization of miRNA targets. These included downregulation of key genes involved in ciliogenesis and was associated with defective multicilia formation both in vivo and in primary airway epithelial cultures. Similar analysis of Tnrc6a disruption in yolk sac showed stabilization of miRNA targets, highlighting the potential diversity of these mechanisms across organs. Nature Publishing Group UK 2023-05-01 /pmc/articles/PMC10151349/ /pubmed/37127654 http://dx.doi.org/10.1038/s41598-023-34365-8 Text en © The Author(s) 2023 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Liu, Helu Li, Huijun Jiang, Zhihua Jin, Shibo Song, Rui Yang, Ying Li, Jun Huang, Jingshu Zhang, Xiaoqing Dong, Xuesong Mori, Munemasa Fritzler, Marvin J. He, Lin Cardoso, Wellington V. Lu, Jining A local translation program regulates centriole amplification in the airway epithelium |
title | A local translation program regulates centriole amplification in the airway epithelium |
title_full | A local translation program regulates centriole amplification in the airway epithelium |
title_fullStr | A local translation program regulates centriole amplification in the airway epithelium |
title_full_unstemmed | A local translation program regulates centriole amplification in the airway epithelium |
title_short | A local translation program regulates centriole amplification in the airway epithelium |
title_sort | local translation program regulates centriole amplification in the airway epithelium |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151349/ https://www.ncbi.nlm.nih.gov/pubmed/37127654 http://dx.doi.org/10.1038/s41598-023-34365-8 |
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