RNA-binding protein 39 (RBM39), also known as splicing factor HCC1, CAPERα, FSAP59, RNPC2, and CAPER alpha, is a pivotal serine/arginine-rich (SR) RNA-binding protein engaged in pre-mRNA splicing, transcription coactivation, and alternative splicing [1]. RBM39 plays a significant role in selective RNA splicing and is under scrutiny as a potential therapeutic target in cancer due to its implication in cancer progression and proliferation [1][2]. Furthermore, RBM39 has been found to influence c-Jun phosphorylation and interact with viral RNA, facilitating the proliferation of porcine reproductive and respiratory syndrome virus (PRRSV) [3][4]. Its domain architecture bears a resemblance to U2AF65, participating in UHM–ULM interactions within the RBM39–U2AF65 splicing-factor complex, underscoring its involvement in splicing regulation [5][6]. RBM39's influence extends to innate immunity modulation through transcriptional and splicing control of key factors [7]. Moreover, RBM39 overexpression has been reported in various cancers like lung cancer and hepatocellular carcinoma, where it regulates alternative splicing [8][9][10]. Additionally, RBM39 facilitates bridging between pre-mRNA, U1, and U2 snRNPs, regulating alternative splicing [9]. Finally, RBM39 is inhibited by the transcription factor c-Jun under genotoxic stress, implying its role in stress response and splicing reprogramming [11].
References:
[1] C. Xu, X. Chen, X. Zhang, D. Zhao, Z. Dou, X. Xieet al., "Rna-binding protein 39: a promising therapeutic target for cancer", Cell Death Discovery, vol. 7, no. 1, 2021. https://doi.org/10.1038/s41420-021-00598-7
[2] R. Zhang, W. Wang, N. Zhang, W. Liu, L. Zhang, & N. Liu, "Systematic pan‐cancer analysis identifies rbm39 as an immunological and prognostic biomarker", Journal of Cellular and Molecular Medicine, vol. 26, no. 18, p. 4859-4871, 2022. https://doi.org/10.1111/jcmm.17517
[3] Y. Song, Y. Guo, X. Li, R. Sun, M. Zhu, J. Shiet al., "Rbm39 alters phosphorylation of c-jun and binds to viral rna to promote prrsv proliferation",, 2020. https://doi.org/10.1101/2020.11.13.382531
[4] Y. Song, Y. Guo, X. Li, R. Sun, M. Zhu, J. Shiet al., "Rbm39 alters phosphorylation of c-jun and binds to viral rna to promote prrsv proliferation", Frontiers in Immunology, vol. 12, 2021. https://doi.org/10.3389/fimmu.2021.664417
[5] G. Stepanyuk, P. Serrano, E. Peralta, C. Farr, H. Axelrod, M. Geraltet al., "Uhm–ulm interactions in the rbm39–u2af65 splicing-factor complex", Acta Crystallographica Section D Structural Biology, vol. 72, no. 4, p. 497-511, 2016. https://doi.org/10.1107/s2059798316001248
[6] S. Mai, X. Qu, P. Li, Q. Ma, C. Cao, & X. Li, "Global regulation of alternative rna splicing by the sr-rich protein rbm39", Biochimica Et Biophysica Acta (Bba) - Gene Regulatory Mechanisms, vol. 1859, no. 8, p. 1014-1024, 2016. https://doi.org/10.1016/j.bbagrm.2016.06.007
[7] T. Li, "Rbm39 shapes innate immunity through transcriptional and splicing control of irf3 and other key factors",, 2023. https://doi.org/10.1101/2023.10.13.562221
[8] Y. Chai, X. Liu, L. Dai, L. Yang, M. Liu, & J. Zhang, "Overexpression of hcc1/caperα may play a role in lung cancer carcinogenesis", Tumor Biology, vol. 35, no. 7, p. 6311-6317, 2014. https://doi.org/10.1007/s13277-014-1819-y
[9] S. Campagne, D. Jutzi, F. Malard, M. Matoga, K. Romane, M. Feldmulleret al., "The cancer-associated rbm39 bridges the pre-mrna, u1 and u2 snrnps to regulate alternative splicing",, 2022. https://doi.org/10.1101/2022.08.30.505862
[10] F. Cui, W. Wang, C. Zhuang, & P. Wang, "Rbm39 is a potential prognostic biomarker associated with immune infiltrates in hepatocellular carcinoma",, 2023. https://doi.org/10.21203/rs.3.rs-2750988/v1
[11] F. Lemaitre, F. Chakrama, T. O'Grady, O. Peulen, G. Rademaker, A. Dewardet al., "The transcription factor c-jun inhibits rbm39 to reprogram pre-mrna splicing during genotoxic stress", Nucleic Acids Research, vol. 50, no. 22, p. 12768-12789, 2022. https://doi.org/10.1093/nar/gkac1130
