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microRNA-mediated regulation of microRNA machinery controls cell fate decisions

microRNAs associate with Argonaute proteins, forming the microRNA-induced silencing complex (miRISC), to repress target gene expression post-transcriptionally. Although microRNAs are critical regulators in mammalian cell differentiation, our understanding of how microRNA machinery, such as the miRIS...

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Autores principales: Liu, Qiuying, Novak, Mariah K, Pepin, Rachel M, Eich, Taylor, Hu, Wenqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504967/
https://www.ncbi.nlm.nih.gov/pubmed/34596044
http://dx.doi.org/10.7554/eLife.72289
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author Liu, Qiuying
Novak, Mariah K
Pepin, Rachel M
Eich, Taylor
Hu, Wenqian
author_facet Liu, Qiuying
Novak, Mariah K
Pepin, Rachel M
Eich, Taylor
Hu, Wenqian
author_sort Liu, Qiuying
collection PubMed
description microRNAs associate with Argonaute proteins, forming the microRNA-induced silencing complex (miRISC), to repress target gene expression post-transcriptionally. Although microRNAs are critical regulators in mammalian cell differentiation, our understanding of how microRNA machinery, such as the miRISC, are regulated during development is still limited. We previously showed that repressing the production of one Argonaute protein, Ago2, by Trim71 is important for mouse embryonic stem cells (mESCs) self-renewal (Liu et al., 2021). Here, we show that among the four Argonaute proteins in mammals, Ago2 is the major developmentally regulated Argonaute protein in mESCs. Moreover, in pluripotency, besides the Trim71-mediated regulation of Ago2 (Liu et al., 2021), Mir182/Mir183 also repress Ago2. Specific inhibition of this microRNA-mediated repression results in stemness defects and accelerated differentiation through the let-7 microRNA pathway. These results reveal a microRNA-mediated regulatory circuit on microRNA machinery that is critical to maintaining pluripotency.
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spelling pubmed-85049672021-10-13 microRNA-mediated regulation of microRNA machinery controls cell fate decisions Liu, Qiuying Novak, Mariah K Pepin, Rachel M Eich, Taylor Hu, Wenqian eLife Cell Biology microRNAs associate with Argonaute proteins, forming the microRNA-induced silencing complex (miRISC), to repress target gene expression post-transcriptionally. Although microRNAs are critical regulators in mammalian cell differentiation, our understanding of how microRNA machinery, such as the miRISC, are regulated during development is still limited. We previously showed that repressing the production of one Argonaute protein, Ago2, by Trim71 is important for mouse embryonic stem cells (mESCs) self-renewal (Liu et al., 2021). Here, we show that among the four Argonaute proteins in mammals, Ago2 is the major developmentally regulated Argonaute protein in mESCs. Moreover, in pluripotency, besides the Trim71-mediated regulation of Ago2 (Liu et al., 2021), Mir182/Mir183 also repress Ago2. Specific inhibition of this microRNA-mediated repression results in stemness defects and accelerated differentiation through the let-7 microRNA pathway. These results reveal a microRNA-mediated regulatory circuit on microRNA machinery that is critical to maintaining pluripotency. eLife Sciences Publications, Ltd 2021-10-01 /pmc/articles/PMC8504967/ /pubmed/34596044 http://dx.doi.org/10.7554/eLife.72289 Text en © 2021, Liu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Liu, Qiuying
Novak, Mariah K
Pepin, Rachel M
Eich, Taylor
Hu, Wenqian
microRNA-mediated regulation of microRNA machinery controls cell fate decisions
title microRNA-mediated regulation of microRNA machinery controls cell fate decisions
title_full microRNA-mediated regulation of microRNA machinery controls cell fate decisions
title_fullStr microRNA-mediated regulation of microRNA machinery controls cell fate decisions
title_full_unstemmed microRNA-mediated regulation of microRNA machinery controls cell fate decisions
title_short microRNA-mediated regulation of microRNA machinery controls cell fate decisions
title_sort microrna-mediated regulation of microrna machinery controls cell fate decisions
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504967/
https://www.ncbi.nlm.nih.gov/pubmed/34596044
http://dx.doi.org/10.7554/eLife.72289
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