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Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development
Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) plays an important role in RNA processing via in m(6)A modification of pre-mRNA or pre-miRNA. However, the functional role of and relationship between m(6)A and hnRNPA2/B1 in early embryonic development are unclear. Here, we found that hnRNP...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572863/ https://www.ncbi.nlm.nih.gov/pubmed/31201338 http://dx.doi.org/10.1038/s41598-019-44714-1 |
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author | Kwon, Jeongwoo Jo, Yu-Jin Namgoong, Suk Kim, Nam-Hyung |
author_facet | Kwon, Jeongwoo Jo, Yu-Jin Namgoong, Suk Kim, Nam-Hyung |
author_sort | Kwon, Jeongwoo |
collection | PubMed |
description | Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) plays an important role in RNA processing via in m(6)A modification of pre-mRNA or pre-miRNA. However, the functional role of and relationship between m(6)A and hnRNPA2/B1 in early embryonic development are unclear. Here, we found that hnRNPA2/B1 is crucial for early embryonic development by virtue of regulating specific gene transcripts. HnRNPA2/B1 was localized to the nucleus and cytoplasm during subsequent embryonic development, starting at fertilization. Knockdown of hnRNPA2/B1 delayed embryonic development after the 4-cell stage and blocked further development. RNA-Seq analysis revealed changes in the global expression patterns of genes involved in transcription, translation, cell cycle, embryonic stem cell differentiation, and RNA methylation in hnRNPA2/B1 KD blastocysts. The levels of the inner cell mass markers OCT4 and SOX2 were decreased in hnRNPA2/B1 KD blastocysts, whereas that of the differentiation marker GATA4 was decreased. N6-Adenosine methyltransferase METTL3 knock-down caused embryonic developmental defects similar to those in hnRNPA2/B1 KD embryos. Moreover, METTL3 KD blastocysts showed increased mis-localization of hnRNPA2/B1 and decreased m(6)A RNA methylation. Taken together, our results suggest that hnRNPA2/B1 is essential for early embryogenesis through the regulation of transcription-related factors and determination of cell fate transition. Moreover, hnRNPA2/B1 is regulated by METTL3-dependent m(6)A RNA methylation. |
format | Online Article Text |
id | pubmed-6572863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65728632019-06-24 Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development Kwon, Jeongwoo Jo, Yu-Jin Namgoong, Suk Kim, Nam-Hyung Sci Rep Article Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) plays an important role in RNA processing via in m(6)A modification of pre-mRNA or pre-miRNA. However, the functional role of and relationship between m(6)A and hnRNPA2/B1 in early embryonic development are unclear. Here, we found that hnRNPA2/B1 is crucial for early embryonic development by virtue of regulating specific gene transcripts. HnRNPA2/B1 was localized to the nucleus and cytoplasm during subsequent embryonic development, starting at fertilization. Knockdown of hnRNPA2/B1 delayed embryonic development after the 4-cell stage and blocked further development. RNA-Seq analysis revealed changes in the global expression patterns of genes involved in transcription, translation, cell cycle, embryonic stem cell differentiation, and RNA methylation in hnRNPA2/B1 KD blastocysts. The levels of the inner cell mass markers OCT4 and SOX2 were decreased in hnRNPA2/B1 KD blastocysts, whereas that of the differentiation marker GATA4 was decreased. N6-Adenosine methyltransferase METTL3 knock-down caused embryonic developmental defects similar to those in hnRNPA2/B1 KD embryos. Moreover, METTL3 KD blastocysts showed increased mis-localization of hnRNPA2/B1 and decreased m(6)A RNA methylation. Taken together, our results suggest that hnRNPA2/B1 is essential for early embryogenesis through the regulation of transcription-related factors and determination of cell fate transition. Moreover, hnRNPA2/B1 is regulated by METTL3-dependent m(6)A RNA methylation. Nature Publishing Group UK 2019-06-14 /pmc/articles/PMC6572863/ /pubmed/31201338 http://dx.doi.org/10.1038/s41598-019-44714-1 Text en © The Author(s) 2019 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 Kwon, Jeongwoo Jo, Yu-Jin Namgoong, Suk Kim, Nam-Hyung Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development |
title | Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development |
title_full | Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development |
title_fullStr | Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development |
title_full_unstemmed | Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development |
title_short | Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development |
title_sort | functional roles of hnrnpa2/b1 regulated by mettl3 in mammalian embryonic development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572863/ https://www.ncbi.nlm.nih.gov/pubmed/31201338 http://dx.doi.org/10.1038/s41598-019-44714-1 |
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