TY - JOUR TI - microRNA-mediated regulation of microRNA machinery controls cell fate decisions AU - Liu, Qiuying AU - Novak, Mariah K AU - Pepin, Rachel M AU - Eich, Taylor AU - Hu, Wenqian A2 - Nilsen, Timothy W A2 - Manley, James L A2 - Patel, Ravi K VL - 10 PY - 2021 DA - 2021/10/01 SP - e72289 C1 - eLife 2021;10:e72289 DO - 10.7554/eLife.72289 UR - https://doi.org/10.7554/eLife.72289 AB - 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. KW - mir-182 KW - mir-183 KW - Ago2 KW - RISC KW - let-7 microrma KW - pluripotency JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -