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. 2021 Aug 20;12:5057. doi: 10.1038/s41467-021-25078-5

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits 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. 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/4.0/.

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Fig. 6 — a–g Association analysis of the distance between a miRNA target site (MTS) and the nearest RBP-binding site (RBS) on the 3′UTR, denoted as d_MTS-RBS, with MT efficacy for different site types, seed-pairing stabilities (SPSs), and various properties of RBPs. A subset of 3′UTRs depicted in Fig. 1d were selected with respect to different site types (a), SPSs (b), function of RBPs on mRNA stability (c), helicase activity (d), strand specificity (e), subcellular localization (f), and previously reported function of RBPs on MT regulation (g). The selected 3′UTRs were split into four subgroups with respect to d_MTS-RBS. Each subgroup was carefully chosen to have statistically indistinguishable confounding features among four subgroups, and mRNA fold changes were compared (see Supplementary Fig. 5b for full versions). Otherwise as in Fig. 1d. h Schematic illustration of the MT mechanism for the MTS that overlaps with an RBS. Before AGO-miRNA complex binds to the MTS, RBPs can bind to their RBS (top). One possible scenario afterwards is that the RBP binding competes against miRNA-bound AGO preventing it from productive MT (bottom left). However, our results support the other scenario where miRNA-bound AGO predominantly replaces mRNA-bound RBPs leading to productive MT (bottom right).