3MDG

Crystal Structure of the 25kDa Subunit of Human Cleavage factor Im in complex with RNA UUGUAU

Summary for 3MDG

• Entry DOI: 10.2210/pdb3mdg/pdb
• Related: 2Cl3 2j8q 3BAP 3BHO 3MDI
• Descriptor: Cleavage and polyadenylation specificity factor subunit 5, RNA (5'-R(*UP*UP*GP*UP*AP*U)-3'), GLYCEROL, ... (4 entities in total)
• Functional Keywords: cpsf5, cf im, mrna processing, cleavage factor, nudix protein, protein-rna complex, rna binding protein, rna binding-rna complex, rna binding/rna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O43809
• Total number of polymer chains: 3
• Total formula weight: 54648.88

Authors

Yang, Q.,Gilmartin, G.M.,Doublie, S. (deposition date: 2010-03-30, release date: 2010-06-02, Last modification date: 2023-09-06)

Primary citation

Yang, Q.,Gilmartin, G.M.,Doublie, S.
Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing.
Proc.Natl.Acad.Sci.USA, 107:10062-10067, 2010

PubMed Abstract: Human Cleavage Factor Im (CFI(m)) is an essential component of the pre-mRNA 3' processing complex that functions in the regulation of poly(A) site selection through the recognition of UGUA sequences upstream of the poly(A) site. Although the highly conserved 25 kDa subunit (CFI(m)25) of the CFI(m) complex possesses a characteristic alpha/beta/alpha Nudix fold, CFI(m)25 has no detectable hydrolase activity. Here we report the crystal structures of the human CFI(m)25 homodimer in complex with UGUAAA and UUGUAU RNA sequences. CFI(m)25 is the first Nudix protein to be reported to bind RNA in a sequence-specific manner. The UGUA sequence contributes to binding specificity through an intramolecular G:A Watson-Crick/sugar-edge base interaction, an unusual pairing previously found to be involved in the binding specificity of the SAM-III riboswitch. The structures, together with mutational data, suggest a novel mechanism for the simultaneous sequence-specific recognition of two UGUA elements within the pre-mRNA. Furthermore, the mutually exclusive binding of RNA and the signaling molecule Ap(4)A (diadenosine tetraphosphate) by CFI(m)25 suggests a potential role for small molecules in the regulation of mRNA 3' processing.

PubMed: 20479262
DOI: 10.1073/pnas.1000848107

Experimental method

X-RAY DIFFRACTION (2.22 Å)