{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSRSF10, also known as SRp38, is a multifunctional splicing regulator whose activity is tightly controlled by its phosphorylation status. Under normal conditions, it is relatively inert as a splicing enhancer; however, in response to cellular stresses such as mitosis and heat shock, SRSF10 becomes dephosphorylated and transforms into a potent general repressor of pre‐mRNA splicing. This stress‐induced dephosphorylation not only disrupts its normal nuclear speckle localization and RNA binding but also interferes with early spliceosome assembly—for instance, by impeding U1 snRNP recognition—thus ensuring rapid transcriptome remodeling under adverse conditions. Notably, maintenance of its phosphorylated state by factors such as Hsp27 is crucial for splicing thermotolerance, preserving normal splicing patterns during mild thermal challenges."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in stress responses, SRSF10 critically modulates alternative splicing decisions that dictate cell fate. It often functions in an antagonistic interplay with other splicing regulators—for example, by counteracting the effects of SRSF3—to influence the inclusion or exclusion of key exons in transcripts governing apoptosis, DNA repair, and cell-cycle progression. In the context of DNA damage, SRSF10 dephosphorylation alters its association with other RNA binding proteins (including diverse hnRNPs), thereby shifting splicing outcomes toward production of pro-apoptotic isoforms such as that of Bcl-x. Moreover, an autoregulatory mechanism mediated by a conserved minor intron ensures a balanced expression of SRSF10 along with other SR proteins, and its binding to splicing silencer elements demonstrates a dosage-sensitive control that has implications for therapeutic strategies targeting splicing defects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe regulatory versatility of SRSF10 also extends to diverse disease settings. Aberrant SRSF10 activity has been linked to oncogenesis; for example, its misregulation promotes the production of splice variants with tumor‐promoting functions in hepatocellular carcinoma and colorectal cancer, where shifts in alternative exon inclusion associate with higher tumor grade. Similarly, in hepatocytes infected by hepatitis B virus, the dephosphorylated SRSF10 exerts an antiviral restriction effect by modulating viral RNA metabolism rather than splicing per se. Altered splicing decisions mediated by SRSF10 further impact pathways involved in cholesterol homeostasis and atherogenesis, while related SR proteins like NSSR1 have also been investigated in colorectal cancer contexts. In addition, evidence from studies in gliomas and even in angiogenesis‐related circuits underscores its broad impact on disease‐associated transcriptome remodeling. Together, these findings identify SRSF10 as a pivotal nexus that integrates stress signals and splicing regulation with significant consequences for cellular homeostasis and disease development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chanseok Shin, James L Manley "}, {"type": "b", "children": [{"type": "t", "text": "The SR protein SRp38 represses splicing in M phase cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(02)01038-3"}], "href": "https://doi.org/10.1016/s0092-8674(02"}, {"type": "t", "text": "01038-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12419250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12419250"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chanseok Shin, Ying Feng, James L Manley "}, {"type": "b", "children": [{"type": "t", "text": "Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature02288"}], "href": "https://doi.org/10.1038/nature02288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14765198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14765198"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chanseok Shin, Frida E Kleiman, James L Manley "}, {"type": "b", "children": [{"type": "t", "text": "Multiple properties of the splicing repressor SRp38 distinguish it from typical SR proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.18.8334-8343.2005"}], "href": "https://doi.org/10.1128/MCB.25.18.8334-8343.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16135820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16135820"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yongsheng Shi, Kensei Nishida, Dafne Campigli Di Giammartino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock-induced SRSF10 dephosphorylation displays thermotolerance mediated by Hsp27."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01123-10"}], "href": "https://doi.org/10.1128/MCB.01123-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21135127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21135127"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xuexia Zhou, Xuebing Li, Yuanming Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms5581"}], "href": "https://doi.org/10.1038/ncomms5581"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25091051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25091051"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wen Xiao, Samir Adhikari, Ujwal Dahal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2016.01.012"}], "href": "https://doi.org/10.1016/j.molcel.2016.01.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26876937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26876937"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lulzim Shkreta, Johanne Toutant, Mathieu Durand, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SRSF10 Connects DNA Damage to the Alternative Splicing of Transcripts Encoding Apoptosis, Cell-Cycle Control, and DNA Repair Factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.10.071"}], "href": "https://doi.org/10.1016/j.celrep.2016.10.071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27851963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27851963"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Alexandre Cloutier, Lulzim Shkreta, Johanne Toutant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hnRNP A1/A2 and Sam68 collaborate with SRSF10 to control the alternative splicing response to oxaliplatin-mediated DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-20360-x"}], "href": "https://doi.org/10.1038/s41598-018-20360-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29396485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29396485"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Stefan Meinke, Gesine Goldammer, A Ioana Weber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Srsf10 and the minor spliceosome control tissue-specific and dynamic SR protein expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.56075"}], "href": "https://doi.org/10.7554/eLife.56075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32338600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32338600"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sabrina B Frederiksen, Lise L Holm, Martin R Larsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of SRSF10 as a regulator of SMN2 ISS-N1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.24149"}], "href": "https://doi.org/10.1002/humu.24149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33300159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33300159"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "I-Fang Ling, Steven Estus "}, {"type": "b", "children": [{"type": "t", "text": "Role of SFRS13A in low-density lipoprotein receptor splicing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21244"}], "href": "https://doi.org/10.1002/humu.21244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20232416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20232416"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Wei Zhang, Quan Shen, Jia-xi Shen "}, {"type": "b", "children": [{"type": "t", "text": "[Expression of neural salient serine-/arginine-rich protein 1 (NSSR1) in colorectal cancer]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhejiang Da Xue Xue Bao Yi Xue Ban (2011)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21984158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21984158"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Xiaobai Liu, Shuyuan Shen, Lu Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-020-01625-8"}], "href": "https://doi.org/10.1186/s13046-020-01625-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32600379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32600379"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hélène Chabrolles, Héloïse Auclair, Serena Vegna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatitis B virus Core protein nuclear interactome identifies SRSF10 as a host RNA-binding protein restricting HBV RNA production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1008593"}], "href": "https://doi.org/10.1371/journal.ppat.1008593"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33180834"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33180834"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Cunjie Chang, Muthukumar Rajasekaran, Yiting Qiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-022-29016-x"}], "href": "https://doi.org/10.1038/s41467-022-29016-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35296659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35296659"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Xiaoming Liu, Yongqiang Zheng, Mengqing Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SRSF10 stabilizes CDC25A by triggering exon 6 skipping to promote hepatocarcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-022-02558-0"}], "href": "https://doi.org/10.1186/s13046-022-02558-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36539837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36539837"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Yuhua Fan, Yue Zhang, Hongrui Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncR-GAS5 upregulates the splicing factor SRSF10 to impair endothelial autophagy, leading to atherogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11684-022-0931-4"}], "href": "https://doi.org/10.1007/s11684-022-0931-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36645633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36645633"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Wenzhe An, Qingqing Yang, Yunlan Xi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of SRSF10 as a promising prognostic biomarker with functional significance among SRSFs for glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2023.122392"}], "href": "https://doi.org/10.1016/j.lfs.2023.122392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38160788"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38160788"}]}]}]}