6dnh
From Proteopedia
Cryo-EM structure of human CPSF-160-WDR33-CPSF-30-PAS RNA complex at 3.4 A resolution
Structural highlights
Function[CPSF1_HUMAN] Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. This subunit is involved in the RNA recognition step of the polyadenylation reaction.[1] [CPSF4_HUMAN] Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U).[2] [3] [WDR33_HUMAN] Essential for both cleavage and polyadenylation of pre-mRNA 3' ends.[4] Publication Abstract from PubMedNearly all eukaryotic messenger RNA precursors must undergo cleavage and polyadenylation at their 3'-end for maturation. A crucial step in this process is the recognition of the AAUAAA polyadenylation signal (PAS), and the molecular mechanism of this recognition has been a long-standing problem. Here, we report the cryo-electron microscopy structure of a quaternary complex of human CPSF-160, WDR33, CPSF-30, and an AAUAAA RNA at 3.4-A resolution. Strikingly, the AAUAAA PAS assumes an unusual conformation that allows this short motif to be bound directly by both CPSF-30 and WDR33. The A1 and A2 bases are recognized specifically by zinc finger 2 (ZF2) of CPSF-30 and the A4 and A5 bases by ZF3. Interestingly, the U3 and A6 bases form an intramolecular Hoogsteen base pair and directly contact WDR33. CPSF-160 functions as an essential scaffold and preorganizes CPSF-30 and WDR33 for high-affinity binding to AAUAAA. Our findings provide an elegant molecular explanation for how PAS sequences are recognized for mRNA 3'-end formation. Molecular basis for the recognition of the human AAUAAA polyadenylation signal.,Sun Y, Zhang Y, Hamilton K, Manley JL, Shi Y, Walz T, Tong L Proc Natl Acad Sci U S A. 2017 Dec 5. pii: 1718723115. doi:, 10.1073/pnas.1718723115. PMID:29208711[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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