| 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] [CPSF6_HUMAN] Component of the cleavage factor Im complex (CFIm) that plays a key role in pre-mRNA 3'-processing. Involved in association with NUDT21/CPSF5 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. CPSF6 binds to cleavage and polyadenylation RNA substrates and promotes RNA looping.[7] [8] [9] [10] [11]
Publication Abstract from PubMed
Cleavage factor I(m) (CFI(m)) is a highly conserved component of the eukaryotic mRNA 3' processing machinery that functions in sequence-specific poly(A) site recognition through the collaboration of a 25 kDa subunit containing a Nudix domain and a larger subunit of 59, 68, or 72 kDa containing an RNA recognition motif (RRM). Our previous work demonstrated that CFI(m)25 is both necessary and sufficient for sequence-specific binding of the poly(A) site upstream element UGUA. Here, we report the crystal structure of CFI(m)25 complexed with the RRM domain of CFI(m)68 and RNA. The CFI(m)25 dimer is clasped on opposite sides by two CFI(m)68 RRM domains. Each CFI(m)25 subunit binds one UGUA element specifically. Biochemical analysis indicates that the CFI(m)68 RRMs serve to enhance RNA binding and facilitate RNA looping. The intrinsic ability of CFI(m) to direct RNA looping may provide a mechanism for its function in the regulation of alternative poly(A) site selection.
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.,Yang Q, Coseno M, Gilmartin GM, Doublie S Structure. 2011 Feb 2. PMID:21295486[12]
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
- ↑ 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, 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
- ↑ 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
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