SERBP1, also known as SERPINE1 mRNA binding protein 1, is an RNA binding protein with mostly disordered structure and lacking canonical RNA-binding domains. It has been implicated in multiple biological functions. SERBP1 is involved in stress granule (SG) clearance, splicing, cell division, ribosome biogenesis, apoptosis regulation, and is associated with processes like DNA repair, ferroptosis, and cellular transformation [1,2,3,4]. It participates in various pathways such as those related to cell proliferation, apoptosis, and metabolic processes, and is thus of great biological importance [3]. Genetic models, especially knockout models, can be valuable in further exploring its functions.

In vivo depletion of SERBP1 in testicular cells leads to increased germ cell apoptosis upon scrotal heat stress, suggesting its role in protecting male germ cells from thermostimuli damage by regulating 26S proteasome activity and G3BP1 ubiquitination to facilitate SG clearance [1]. In HeLa cells, overexpression of SERBP1 induces apoptosis by regulating the expression and alternative splicing of genes related to cell proliferation, apoptosis, and metabolic processes [3]. KSHV-encoded vIL-6 promotes SIRT3-induced deacetylation of SERBP1, which in turn inhibits ferroptosis and enhances cellular transformation [4]. In neurons, silencing SERBP1 relieves KCC2 repression by miR-92 [5]. In S phase, SERBP1 affects homologous recombination-mediated DNA repair by regulating CtIP translation [6]. Also, SYT1 binds to and stabilizes SERBP1, up-regulating SERBP1/GLUT2 expression to antagonize paraquat intracellular accumulation and nephrocyte toxicity [7].

In conclusion, SERBP1 has diverse essential biological functions. Model-based research, especially through gene knockout models in different cell types and tissues, has revealed its role in protecting germ cells from heat stress, regulating apoptosis in cancer cells, influencing ferroptosis and cellular transformation in virus-associated cancers, modulating gene silencing in neurons, facilitating DNA repair, and preventing paraquat-induced nephrotoxicity. These findings contribute to understanding the mechanisms of related diseases and potentially developing new therapeutic strategies.

References:

1. Wang, Fengli, Wang, Lingjuan, Gan, Shiming, Wang, Xiaoli, Yuan, Shuiqiao. 2023. SERBP1 Promotes Stress Granule Clearance by Regulating 26S Proteasome Activity and G3BP1 Ubiquitination and Protects Male Germ Cells from Thermostimuli Damage. In Research (Washington, D.C.), 6, 0091. doi:10.34133/research.0091. https://pubmed.ncbi.nlm.nih.gov/37223481/

2. Breunig, Kira, Lei, Xiufen, Montalbano, Mauro, Galante, Pedro A F, Penalva, Luiz O F. 2024. SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.03.22.586270. https://pubmed.ncbi.nlm.nih.gov/38585848/

3. Zhou, Junjie, Chen, Wenhao, He, Qianwen, Ding, Zhao, Qian, Qun. 2022. SERBP1 affects the apoptotic level by regulating the expression and alternative splicing of cellular and metabolic process genes in HeLa cells. In PeerJ, 10, e14084. doi:10.7717/peerj.14084. https://pubmed.ncbi.nlm.nih.gov/36213507/

4. Zhou, Jing, Wang, Tianjiao, Zhang, Haoran, Gao, Shou-Jiang, Lu, Chun. 2024. KSHV vIL-6 promotes SIRT3-induced deacetylation of SERBP1 to inhibit ferroptosis and enhance cellular transformation by inducing lipoyltransferase 2 mRNA degradation. In PLoS pathogens, 20, e1012082. doi:10.1371/journal.ppat.1012082. https://pubmed.ncbi.nlm.nih.gov/38470932/

5. Barbato, Christian, Frisone, Paola, Braccini, Laura, Cogoni, Carlo, Ruberti, Francesca. 2022. Silencing of Ago-2 Interacting Protein SERBP1 Relieves KCC2 Repression by miR-92 in Neurons. In Cells, 11, . doi:10.3390/cells11061052. https://pubmed.ncbi.nlm.nih.gov/35326503/

6. Ahn, Jang-Won, Kim, Sunjik, Na, Wooju, Kim, Seon-Young, Choi, Cheol Yong. 2015. SERBP1 affects homologous recombination-mediated DNA repair by regulation of CtIP translation during S phase. In Nucleic acids research, 43, 6321-33. doi:10.1093/nar/gkv592. https://pubmed.ncbi.nlm.nih.gov/26068472/

7. Yin, Ran, Ke, Jingjing, Zhao, Mingming, Dai, Xiaoqin, Hong, Guangliang. 2024. Synaptotagmin-1 antagonizes paraquat intracellular accumulation and nephrocyte toxicity by up-regulating SERBP1/GLUT2 expression. In Chemico-biological interactions, 400, 111165. doi:10.1016/j.cbi.2024.111165. https://pubmed.ncbi.nlm.nih.gov/39059605/