NUDT21, also known as CFIm25 or CPSF5, is a crucial RNA-binding protein. It is involved in alternative mRNA polyadenylation (APA), a process that generates diverse 3' ends of RNA polymerase II transcripts. APA can result in mRNA isoforms with different 3' UTR lengths, influencing gene expression. NUDT21 binds to UGUA sequences of precursor RNAs and is associated with multiple biological processes and disease-related pathways [3,6].

In B-cell acute lymphoblastic leukemia (B-ALL), NUDT21 deletion increased CD19 expression and sensitivity to CD19-specific immunotherapies, suggesting it limits CD19 levels through APA [1]. In renal fibrosis, TRIM65 interacts with NUDT21 to induce its degradation, altering the 3'UTR-APA of pro-fibrotic genes. Reducing NUDT21 expression exacerbated renal fibrosis [2]. In pancreatic cancer, NUDT21 promoted the usage of proximal polyadenylation sites on MZT1 mRNA, contributing to cancer progression [4]. In glioma, NUDT21-knockdown led to 3'UTR shortening of LAMC1, promoting cell migration [5]. In breast cancer, NUDT21 suppressed tumorigenesis by regulating CPSF6 expression [7].

In summary, NUDT21 is essential in regulating gene expression via APA. Studies using gene-knockout models in various disease areas such as leukemia, fibrosis, and multiple cancers have revealed its role in disease-related biological processes. These findings offer potential new targets for disease treatment and prevention.