biostudies-literatureUnknown136(3)Gu YThe regulation of the programmed cell death protein 1 (PD-1) gene, PDCD1, has been widely explored at transcription and posttranslational levels in T cell function and tumor immune evasion. However, the mechanism for PDCD1 dysregulation at the posttranscriptional level remains largely unknown. Here, we identify protein arginine methyltransferase 5 (PRMT5) as a RNA binding protein in a methyltransferase activity-independent manner, which promotes PDCD1 decay with WD repeat domain 77 protein (WDR77) and Argonaute2. Furthermore, the type-I IFN/STAT1 pathway transcriptionally activates PRMT5 and WDR77, thus enhancing PRMT5/WDR77 binding on a conserved AU-rich element of PDCD1 3' UTR. Functionally, conditional knockout of either PRMT5 or WDR77 in T cells disrupts T cell effector function and seThe Journal of clinical investigatione191469https://www.ebi.ac.uk/biostudies/studies/S-EPMC12867141biostudies-literaturePosttranscriptional regulation of PD-1 by PRMT5/WDR77 complex shapes T cell effector function and antitumor immunity.PMC12867141Tang ZHuang CPan YGu YZhang QYang FZhao XPan CPang QZang HZhang YChen YZhu XWang XGao SfalsePosttranscriptional regulation of PD-1 by PRMT5/WDR77 complex shapes T cell effector function and antitumor immunity.The regulation of the programmed cell death protein 1 (PD-1) gene, PDCD1, has been widely explored at transcription and posttranslational levels in T cell function and tumor immune evasion. However, the mechanism for PDCD1 dysregulation at the posttranscriptional level remains largely unknown. Here, we identify protein arginine methyltransferase 5 (PRMT5) as a RNA binding protein in a methyltransferase activity-independent manner, which promotes PDCD1 decay with WD repeat domain 77 protein (WDR77) and Argonaute2. Furthermore, the type-I IFN/STAT1 pathway transcriptionally activates PRMT5 and WDR77, thus enhancing PRMT5/WDR77 binding on a conserved AU-rich element of PDCD1 3' UTR. Functionally, conditional knockout of either PRMT5 or WDR77 in T cells disrupts T cell effector function and se2026-01-01T00:00:00Z2026 Feb2026-07-15T13:57:07.715Z2026-07-05T03:12:21.062ZS-EPMC128671414162318310.1172/JCI191469