Structural highlights
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
Cleavage factor I(m) is an essential component of the pre-messenger RNA 3'-end processing machinery in higher eukaryotes, participating in both the polyadenylation and cleavage steps. Cleavage factor I(m) is an oligomer composed of a small 25 kDa subunit (CF I(m)25) and a variable larger subunit of either 59, 68 or 72 kDa. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein. These protein-protein interactions are thought to be facilitated by the Nudix domain of CF I(m)25, a hydrolase motif with a characteristic alpha/beta/alpha fold and a conserved catalytic sequence or Nudix box. We present here the crystal structures of human CF I(m)25 in its free and diadenosine tetraphosphate (Ap(4)A) bound forms at 1.85 and 1.80 A, respectively. CF I(m)25 crystallizes as a dimer and presents the classical Nudix fold. Results from crystallographic and biochemical experiments suggest that CF I(m)25 makes use of its Nudix fold to bind but not hydrolyze ATP and Ap(4)A. The complex and apo protein structures provide insight into the active oligomeric state of CF I(m) and suggest a possible role of nucleotide binding in either the polyadenylation and/or cleavage steps of pre-messenger RNA 3'-end processing.
Crystal structure of the 25 kDa subunit of human cleavage factor Im.,Coseno M, Martin G, Berger C, Gilmartin G, Keller W, Doublie S Nucleic Acids Res. 2008 Jun;36(10):3474-83. Epub 2008 Apr 29. PMID:18445629[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Coseno M, Martin G, Berger C, Gilmartin G, Keller W, Doublie S. Crystal structure of the 25 kDa subunit of human cleavage factor Im. Nucleic Acids Res. 2008 Jun;36(10):3474-83. Epub 2008 Apr 29. PMID:18445629 doi:10.1093/nar/gkn079
