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. 2018 Feb 15;25(9):1581–1597. doi: 10.1038/s41418-018-0063-1

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© ADMC Associazione Differenziamento e Morte Cellulare 2018

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits any non-commercial 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. If you remix, transform, or build upon this article or a part thereof, you must distribute your contributions under the same license as the original. 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-nc-sa/4.0/.

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Fig. 8 — A model of mamiRs and JNK/MAPK signaling forming a double-negative feedback regulatory network in skeletal muscle development. a In undifferentiated myoblasts, when JNK/MAPK signaling is activated, it phosphorylates its downstream effector c-Jun. P-c-Jun enters into the nucleus, and together with Fos or ATF family proteins forms a demeric compound that called AP-1 that can could inhibit MyoD transcription, therefore, blocking differentiation. b In differentiated muscle, the activity of JNK/MAPK signaling is attenuated because its key factors are targeted by mamiRs (miR-1a-3p, 133a-3p, 133b-3p, 206-3p, 128-3p, and 351-5p), c-Jun is rarely phosphorylated, so forms less AP-1 compound in nucleus and turns on MyoD transcription, activating the transcription of mamiR genes. In turn, mature mamiRs further repress the JNK/MAPK signaling, forming a double-negative feedback regulatory network in skeletal muscle development