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. 2024 Apr 10;25(5):2220–2238. doi: 10.1038/s44319-024-00128-3

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© The Author(s) 2024

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.

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(A,B) Location of mis-phosphorylated sites across SF3B1 (A) and RBM39 (B) proteins. Functionally relevant protein regions according to UniProt are shown. Significantly changing phosphosites in response to LB-100 are highlighted in red. (C) Motif RNA map shows SF3B4 binding in the proximity of excluded (DOWN), included (UP), or not affected (NO) exons in LB-100-treated as compared to untreated SW-480 colorectal adenocarcinoma cells. (D) Venn diagram shows a significant overlap between AS transcripts in LB-100-treated SW-480 cells, SF3B1-depleted MYC-expressing Human Diploid Fibroblasts (HDF) (Cieśla et al, 2023), indisulam-treated melanomas (Lu et al, 2021), and RBM39 knock-down (KD) SK-N-AS neuroblastoma cell line (Singh et al, 2021). (E) Synergy matrices show cooperativity between LB-100 and pladienolide B and indisulam in the SW-480 human adenocarcinoma cell line. Representative heat map for n = 3 biological replicates. A schematic representation of the experiment is shown on top. Data information: In (D) statistical significance was calculated with hypergeometric test, ****p < 0.0001. See also Fig. EV4. Source data are available online for this figure.