Pabpc4-KO Mouse

Pabpc4, short for poly(A)-binding protein cytoplasmic 4, is an RNA-processing protein. It belongs to the family of cytoplasmic poly(A)-binding proteins (PABPs) and plays a crucial role in promoting gene expression by enhancing translation and mRNA stability. It is involved in multiple biological processes such as energy metabolism, cell differentiation, and antiviral defense [1-3].

In the context of coronavirus replication, Pabpc4 can be regulated by transcription factor SP1 and broadly inhibits the replication of coronaviruses from four genera. It targets the nucleocapsid (N) protein, recruits the E3 ubiquitin ligase MARCH8/MARCHF8 for ubiquitination of the N protein. The ubiquitinated N protein is then recognized by the cargo receptor NDP52/CALCOCO2 and delivered to autolysosomes for degradation, impairing viral proliferation [1,4]. In 3T3-L1 pre-adipocytes, knockdown experiments suggest that Pabpc4 contributes to regulating differentiation and energy metabolism [2]. In C2C12 and MEF cells, silencing of Pabpc4 induces an oxidative phenotype, as it increases the ubiquitination and degradation of NCoR1, derepressing PPAR-regulated genes [3].

In summary, Pabpc4 is essential for gene expression regulation and is involved in various biological processes. Its role in inhibiting coronavirus replication, regulating adipocyte differentiation and energy metabolism, as well as modulating the metabolic stress response has been revealed through functional studies including knockdown and silencing experiments. These findings contribute to our understanding of antiviral strategies, diabetes-related metabolic processes, and potential treatments for metabolic diseases [1-4].

References:

1. Jiao, Yajuan, Kong, Ning, Wang, Hua, Tong, Guangzhi, Shan, Tongling. 2021. PABPC4 Broadly Inhibits Coronavirus Replication by Degrading Nucleocapsid Protein through Selective Autophagy. In Microbiology spectrum, 9, e0090821. doi:10.1128/Spectrum.00908-21. https://pubmed.ncbi.nlm.nih.gov/34612687/

2. Tang, Haibo, Wang, Jie, Deng, Peizhi, Zhu, Shaihong, Lu, Yao. 2023. Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes. In Diabetologia, 66, 2087-2100. doi:10.1007/s00125-023-05978-5. https://pubmed.ncbi.nlm.nih.gov/37540242/

3. Oliveira, A G, Oliveira, L D, Cruz, M V, Auwerx, J, Silveira, L R. 2023. Interaction between poly(A)-binding protein PABPC4 and nuclear receptor corepressor NCoR1 modulates a metabolic stress response. In The Journal of biological chemistry, 299, 104702. doi:10.1016/j.jbc.2023.104702. https://pubmed.ncbi.nlm.nih.gov/37059182/

4. Zhao, Chenchen, Qin, Yan, Huang, Haixin, Lan, Tian, Sun, Wenchao. 2025. PABPC4 Inhibits SADS-CoV Replication by Degrading the Nucleocapsid Protein Through Selective Autophagy. In Veterinary sciences, 12, . doi:10.3390/vetsci12030257. https://pubmed.ncbi.nlm.nih.gov/40266995/