Proteopedia

3mdg

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

Structural highlights

3mdg is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.22Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CPSF5_HUMAN Component of the cleavage factor Im (CFIm) complex that plays a key role in pre-mRNA 3'-processing. Involved in association with CPSF6 or CPSF7 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. NUDT21/CPSF5 binds to cleavage and polyadenylation RNA substrates. The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA. Binds to, but does not hydrolyze mono- and di-adenosine nucleotides. May have a role in mRNA export.[1] [2] [3] [4] [5] [6]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing.,Yang Q, Gilmartin GM, Doublie S Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10062-7. Epub 2010 May 17. PMID:20479262[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Ruegsegger U, Blank D, Keller W. Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits. Mol Cell. 1998 Jan;1(2):243-53. PMID:9659921
  2. ↑ Ruegsegger U, Beyer K, Keller W. Purification and characterization of human cleavage factor Im involved in the 3' end processing of messenger RNA precursors. J Biol Chem. 1996 Mar 15;271(11):6107-13. PMID:8626397
  3. ↑ Brown KM, Gilmartin GM. A mechanism for the regulation of pre-mRNA 3' processing by human cleavage factor Im. Mol Cell. 2003 Dec;12(6):1467-76. PMID:14690600
  4. ↑ Kim S, Yamamoto J, Chen Y, Aida M, Wada T, Handa H, Yamaguchi Y. Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells. 2010 Sep 1;15(9):1003-13. doi: 10.1111/j.1365-2443.2010.01436.x., Epub 2010 Jul 29. PMID:20695905 doi:10.1111/j.1365-2443.2010.01436.x
  5. ↑ Yang Q, Gilmartin GM, 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 U S A. 2010 Jun 1;107(22):10062-7. Epub 2010 May 17. PMID:20479262
  6. ↑ Yang Q, Coseno M, Gilmartin GM, Doublie S. Crystal Structure of a Human Cleavage Factor CFI(m)25/CFI(m)68/RNA Complex Provides an Insight into Poly(A) Site Recognition and RNA Looping. Structure. 2011 Feb 2. PMID:21295486 doi:10.1016/j.str.2010.12.021
  7. ↑ Yang Q, Gilmartin GM, 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 U S A. 2010 Jun 1;107(22):10062-7. Epub 2010 May 17. PMID:20479262

3mdg, resolution 2.22Å

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