NUDT21 knockdown PAS-seq in neuroblastoma I

However, the role of alternative 3′ UTRs in neurolastoma (NB) remains elusive. Here, we show that NUDT21 knockdown inhibits NB cell proliferation, induces cycle arrest/apoptosis in vitro, and suppresses xenograft growth in nude mice.

Mechanistically, NUDT21 silencing triggers global APA dynamics, with ∼85% of APA genes switching to proximal poly(A) sites, shortening 3′ UTRs. Integrative PAS-seq/RNA-seq analyses reveal that NUDT21 regulates E2F targets (e.g., MKI67) via APA. Additionally, NUDT21 occupies gene regulatory regions to directly activate E2F target transcription.