Srsf5, also known as serine and arginine-rich splicing factor 5, is a key regulator in pre-mRNA alternative splicing. It participates in multiple biological processes and is involved in various pathways. For instance, it is associated with the regulation of cell growth, development, and disease-related processes, and genetic models such as knockout mice are valuable for studying its functions [1-10].

In colorectal cancer, LINC01852 inhibits tumorigenesis and chemoresistance by increasing TRIM72-mediated ubiquitination and degradation of SRSF5, thus suppressing SRSF5-mediated alternative splicing of PKM [1]. In pancreatic cancer, the CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, promoting growth and metastasis [2]. In ER-positive breast cancer, SRSF5 modulates tamoxifen resistance by regulating the expression of BQ323636.1 [3]. For influenza A virus, SRSF5-mediated alternative splicing of the M gene is essential for viral replication [4]. In heart development, Srsf5 knockout mice exhibit cardiac dysfunction with non-compaction of the ventricular myocardium due to disrupted alternative splicing of Myom1 [5]. In oral squamous cell carcinoma, SRSF5 functions as an oncogenic splicing factor, and its overexpression promotes cell proliferation and tumor formation [6].

In conclusion, Srsf5 is crucial in regulating alternative splicing, influencing various biological processes and disease conditions. The use of Srsf5 knockout or conditional knockout mouse models has provided valuable insights into its roles in cancer, viral replication, and heart development, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Bian, Zehua, Yang, Fan, Xu, Peiwen, Fei, Bojian, Huang, Zhaohui. 2024. LINC01852 inhibits the tumorigenesis and chemoresistance in colorectal cancer by suppressing SRSF5-mediated alternative splicing of PKM. In Molecular cancer, 23, 23. doi:10.1186/s12943-024-01939-7. https://pubmed.ncbi.nlm.nih.gov/38263157/

2. Chen, Shi, Yang, Can, Wang, Zu-Wei, Shen, Bai-Yong, Wang, Yao-Dong. 2021. CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer. In Journal of hematology & oncology, 14, 60. doi:10.1186/s13045-021-01072-8. https://pubmed.ncbi.nlm.nih.gov/33849617/

3. Tsoi, Ho, Fung, Nicholas Nok-Ching, Man, Ellen P S, Chan, Sum-Yin, Khoo, Ui-Soon. 2023. SRSF5 Regulates the Expression of BQ323636.1 to Modulate Tamoxifen Resistance in ER-Positive Breast Cancer. In Cancers, 15, . doi:10.3390/cancers15082271. https://pubmed.ncbi.nlm.nih.gov/37190199/

4. Li, Qiuchen, Jiang, Zhimin, Ren, Shuning, Chang, Kin-Chow, Liu, Jinhua. 2022. SRSF5-Mediated Alternative Splicing of M Gene is Essential for Influenza A Virus Replication: A Host-Directed Target Against Influenza Virus. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 9, e2203088. doi:10.1002/advs.202203088. https://pubmed.ncbi.nlm.nih.gov/36257906/

5. Zhang, Xiaoli, Wang, Ze, Xu, Qing, Zhang, Lingqiang, Cui, Chun-Ping. 2021. Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium. In iScience, 24, 103097. doi:10.1016/j.isci.2021.103097. https://pubmed.ncbi.nlm.nih.gov/34622152/

6. Yang, Sisi, Jia, Rong, Bian, Zhuan. 2018. SRSF5 functions as a novel oncogenic splicing factor and is upregulated by oncogene SRSF3 in oral squamous cell carcinoma. In Biochimica et biophysica acta. Molecular cell research, 1865, 1161-1172. doi:10.1016/j.bbamcr.2018.05.017. https://pubmed.ncbi.nlm.nih.gov/29857020/