Prpf40b-KO Mouse

Prpf40b, the pre-mRNA processing factor 40 homolog B, is a splicing factor. It is involved in the regulation of alternative splicing, an essential process for increasing the complexity of proteins encoded in the genome [2,3]. As an ortholog of yeast Prp40, it is part of the U1 small nuclear ribonucleoprotein and participates in the initial splice-site recognition during spliceosome assembly [1,2,3].

In K562 cell line, a full Prpf40b knockout (KO) generated by CRISPR/Cas9 technology showed that Prpf40b regulates hundreds of alternative splicing targets. Loss of Prpf40b led to a net increase in exon inclusion, suggesting it mainly acts as a repressor of splicing. It also induced a KLF1 transcriptional signature, with genes involved in iron metabolism and hypoxia, including related pathways like cholesterol biosynthesis and Akt/MAPK signaling. In acute myeloid leukemia, Prpf40b is lowly expressed, and its low expression might contribute to leukemogenesis [1]. Moreover, in cervical cancer cell lines (Hela and Siha), knockdown of Prpf40b inhibits cell proliferation, migration and invasion [4].

In summary, Prpf40b is a key splicing factor regulating alternative splicing. Through gene-knockout models in cell lines, its role in regulating hypoxia-related gene expression in myeloid cells and its potential contribution to leukemogenesis, as well as its impact on cervical cancer cell behavior, have been revealed. These findings help to understand the biological functions of Prpf40b in disease-related processes.

References:

1. Lorenzini, Paolo Alberto, Chew, Resilind Su Ern, Tan, Cheryl Weiqi, Zheng, Jie, Roca, Xavier. 2019. Human PRPF40B regulates hundreds of alternative splicing targets and represses a hypoxia expression signature. In RNA (New York, N.Y.), 25, 905-920. doi:10.1261/rna.069534.118. https://pubmed.ncbi.nlm.nih.gov/31088860/

2. Becerra, Soraya, Montes, Marta, Hernández-Munain, Cristina, Suñé, Carlos. 2015. Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65 and modulates alternative pre-mRNA splicing in vivo. In RNA (New York, N.Y.), 21, 438-57. doi:10.1261/rna.047258.114. https://pubmed.ncbi.nlm.nih.gov/25605964/

3. Becerra, Soraya, Andrés-León, Eduardo, Prieto-Sánchez, Silvia, Hernández-Munain, Cristina, Suñé, Carlos. 2015. Prp40 and early events in splice site definition. In Wiley interdisciplinary reviews. RNA, 7, 17-32. doi:10.1002/wrna.1312. https://pubmed.ncbi.nlm.nih.gov/26494226/

4. Chen, Xiaomei, Dong, Xunhu, Li, Hong, Hao, Lingji, Zhang, Zhe. 2024. RNA-binding proteins signature is a favorable biomarker of prognosis, immunotherapy and chemotherapy response for cervical cancer. In Cancer cell international, 24, 80. doi:10.1186/s12935-024-03257-w. https://pubmed.ncbi.nlm.nih.gov/38383371/