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TitleMolecular basis for the recognition of the human AAUAAA polyadenylation signal.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 115, Issue 7, Page E1419-E1428, Year 2018
Publish dateFeb 13, 2018
AuthorsYadong Sun / Yixiao Zhang / Keith Hamilton / James L Manley / Yongsheng Shi / Thomas Walz / Liang Tong /
PubMed AbstractNearly 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 ...Nearly 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-Å 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.
External linksProc Natl Acad Sci U S A / PubMed:29208711 / PubMed Central
MethodsEM (single particle)
Resolution3.36 - 3.8 Å
Structure data

7112

6dnh

EMDB-7112, PDB-6dnh:
Cryo-EM structure of human CPSF-160-WDR33-CPSF-30-PAS RNA complex at 3.4 A resolution
Method: EM (single particle) / Resolution: 3.4 Å

7113

6bly

EMDB-7113: Cryo-EM structure of human CPSF-160-WDR33 complex at 3.36 A resolution
PDB-6bly: Cryo-EM structure of human CPSF-160-WDR33 complex at 3.36A resolution
Method: EM (single particle) / Resolution: 3.36 Å

7114

6bm0

EMDB-7114, PDB-6bm0:
Cryo-EM structure of human CPSF-160-WDR33 complex at 3.8 A resolution
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • simian virus 40
KeywordsPROTEIN BINDING / polyadenylation / scaffolding protein / WD40 / RNA BINDING PROTEIN/RNA / Recognition of the AAUAAA polyadenylation signal (PAS) / Hoogsteen base pair / zinc finger / RNA BINDING PROTEIN-RNA complex

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