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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doaj-a556999ced3e45f7b4e329f40a75f8e02021-10-11T09:31:39ZengeLife Sciences Publications LtdeLife2050-084X2021-10-011010.7554/eLife.72289microRNA-mediated regulation of microRNA machinery controls cell fate decisionsQiuying Liu0https://orcid.org/0000-0002-1474-4487Mariah K Novak1Rachel M Pepin2Taylor Eich3Wenqian Hu4https://orcid.org/0000-0003-3577-3604Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesmicroRNAs 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.https://elifesciences.org/articles/72289mir-182mir-183Ago2RISClet-7 micrormapluripotency |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qiuying Liu Mariah K Novak Rachel M Pepin Taylor Eich Wenqian Hu |
spellingShingle |
Qiuying Liu Mariah K Novak Rachel M Pepin Taylor Eich Wenqian Hu microRNA-mediated regulation of microRNA machinery controls cell fate decisions eLife mir-182 mir-183 Ago2 RISC let-7 microrma pluripotency |
author_facet |
Qiuying Liu Mariah K Novak Rachel M Pepin Taylor Eich Wenqian Hu |
author_sort |
Qiuying Liu |
title |
microRNA-mediated regulation of microRNA machinery controls cell fate decisions |
title_short |
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_sort |
microrna-mediated regulation of microrna machinery controls cell fate decisions |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-10-01 |
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. |
topic |
mir-182 mir-183 Ago2 RISC let-7 microrma pluripotency |
url |
https://elifesciences.org/articles/72289 |
work_keys_str_mv |
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