WDR33 is an essential component of the mammalian polyadenylation specificity factor (mPSF) complex that directly recognizes the AAUAAA polyadenylation signal during mRNA 3'-end processing 12. The canonical WDR33v1 isoform functions in the nucleus as part of a quaternary complex with CPSF-160, CPSF-30, and Fip1 that binds AAUAAA with ~3 nM affinity 3. Structural studies reveal that WDR33 directly contacts the U3 and A6 bases of AAUAAA through an unusual RNA conformation involving an intramolecular Hoogsteen base pair, while CPSF-160 serves as a scaffold to preorganize the complex for high-affinity binding 4. WDR33 is required for both AAUAAA-dependent polyadenylation and can be specifically UV cross-linked to polyadenylation signals in vivo 1. The WDR33 gene produces three major isoforms through alternative polyadenylation, with the non-canonical isoforms V2 and V3 lacking complete WD repeat domains and functioning in innate immunity rather than mRNA processing 5. WDR33 also plays a role in competitive binding interactions that can regulate other mRNA processing events, as demonstrated in glioblastoma where SNORD51 competes with ZBED6 pre-mRNA for WDR33 binding 6.