microRNA-mediated regulation of microRNA machinery controls cell fate decisions
- Mayo Clinic, United States
Abstract
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 (mESC) 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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-5.
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Studies on Trim71 in mouse embryonic stem cellsNCBI Gene Expression Omnibus | GSE138284.
Article and author information
Author details
Funding
Mayo Foundation for Medical Education and Research
- Qiuying Liu
- Mariah K Novak
- Rachel M Pepin
- Taylor Eich
- Wenqian Hu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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microRNA-mediated regulation of microRNA machinery controls cell fate decisions
eLife 10:e72289.
https://doi.org/10.7554/eLife.72289
