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PMID: 18688255 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3'-end maturation.

EMBO reports ·Vol. 9 ·No. 10 ·2008-10-00 ·Pages 1013-8

Kolev NG, Yario TA, Benson E, Steitz JA

Abstract

In eukaryotes, the process of messenger RNA 3'-end formation involves endonucleolytic cleavage of the transcript followed by synthesis of the poly(A) tail. The complex machinery involved in this maturation process contains two proteins of the metallo-beta-lactamase (MBL) superfamily, the 73 and 100 kDa subunits of the cleavage and polyadenylation specificity factor (CPSF). By using an in vitro system to assess point mutations in these two mammalian proteins, we found that conserved residues from the MBL motifs of both polypeptides are required for assembly of the endonuclease activity that cleaves histone pre-mRNAs. This indicates that CPSF73 and CPSF100 act together in the process of maturation of eukaryotic pre-messenger RNAs, similar to other members of the MBL family, RNases Z and J, which function as homodimers.

MeSH Terms
Amino Acid Motifs/physiology Amino Acid Sequence Base Sequence Cell Line Cleavage And Polyadenylation Specificity Factor/chemistry,genetics,physiology Conserved Sequence/physiology Endonucleases/metabolism,physiology Enzyme Activation/genetics HeLa Cells Histones/biosynthesis,genetics Humans Molecular Sequence Data Protein Structure, Tertiary Protein Subunits/genetics,physiology RNA 3' End Processing/genetics RNA Precursors/metabolism RNA, Messenger/metabolism
Chemicals
Cleavage And Polyadenylation Specificity Factor Histones Protein Subunits RNA Precursors RNA, Messenger Endonucleases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kolev Nikolay G
Howard Hughes Medical Institute, Yale University, 295 Congress Avenue, New Haven, Connecticut 06519, USA.
Yario Therese A
Benson Eleni
Steitz Joan A
References (21)
21 references, click to expand
  1. Symplekin and multiple other polyadenylation factors participate in 3'-end maturation of histone mRNAs.
    Genes Dev. 2005 Nov 1;19(21):2583-92 PMID: 16230528
  2. Symplekin, a novel type of tight junction plaque protein.
    J Cell Biol. 1996 Aug;134(4):1003-18 PMID: 8769423
  3. A genome-wide RNA interference screen reveals that variant histones are necessary for replication-dependent histone pre-mRNA processing.
    Mol Cell. 2007 Nov 30;28(4):692-9 PMID: 18042462
  4. Protein factors in pre-mRNA 3'-end processing.
    Cell Mol Life Sci. 2008 Apr;65(7-8):1099-122 PMID: 18158581
  5. The polyadenylation factor CPSF-73 is involved in histone-pre-mRNA processing.
    Cell. 2005 Oct 7;123(1):37-48 PMID: 16213211
  6. Temporal order of RNA-processing reactions in trypanosomes: rapid trans splicing precedes polyadenylation of newly synthesized tubulin transcripts.
    Mol Cell Biol. 1993 Jan;13(1):720-5 PMID: 8417363
  7. Formation of the 3' end of histone mRNA: getting closer to the end.
    Gene. 2007 Jul 15;396(2):373-90 PMID: 17531405
  8. Generation of histone mRNA 3' ends by endonucleolytic cleavage of the pre-mRNA in a snRNP-dependent in vitro reaction.
    EMBO J. 1986 Jun;5(6):1319-26 PMID: 3015597
  9. Crystal structure of TTHA0252 from Thermus thermophilus HB8, a RNA degradation protein of the metallo-beta-lactamase superfamily.
    J Biochem. 2006 Oct;140(4):535-42 PMID: 16945939
  10. An evolutionary classification of the metallo-beta-lactamase fold proteins.
    In Silico Biol. 1999;1(2):69-91 PMID: 11471246
  11. Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.
    Nature. 2006 Dec 14;444(7121):953-6 PMID: 17128255
  12. 5'-to-3' exoribonuclease activity in bacteria: role of RNase J1 in rRNA maturation and 5' stability of mRNA.
    Cell. 2007 May 18;129(4):681-92 PMID: 17512403
  13. When all's zed and done: the structure and function of RNase Z in prokaryotes.
    Nat Rev Microbiol. 2007 Apr;5(4):278-86 PMID: 17363966
  14. Evidence that polyadenylation factor CPSF-73 is the mRNA 3' processing endonuclease.
    RNA. 2004 Apr;10(4):565-73 PMID: 15037765
  15. A CPSF-73 homologue is required for cell cycle progression but not cell growth and interacts with a protein having features of CPSF-100.
    Mol Cell Biol. 2005 Feb;25(4):1489-500 PMID: 15684398
  16. A complex containing CstF-64 and the SL2 snRNP connects mRNA 3' end formation and trans-splicing in C. elegans operons.
    Genes Dev. 2001 Oct 1;15(19):2562-71 PMID: 11581161
  17. Metallo-beta-lactamase fold within nucleic acids processing enzymes: the beta-CASP family.
    Nucleic Acids Res. 2002 Aug 15;30(16):3592-601 PMID: 12177301
  18. Variable effects of the conserved RNA hairpin element upon 3' end processing of histone pre-mRNA in vitro.
    Nucleic Acids Res. 1993 Apr 11;21(7):1569-75 PMID: 8479907
  19. Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II.
    Cell. 2005 Oct 21;123(2):265-76 PMID: 16239144
  20. Nucleases of the metallo-beta-lactamase family and their role in DNA and RNA metabolism.
    Crit Rev Biochem Mol Biol. 2007 Mar-Apr;42(2):67-93 PMID: 17453916
  21. Structural insights into the dual activity of RNase J.
    Nat Struct Mol Biol. 2008 Feb;15(2):206-12 PMID: 18204464
Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-3178
DOI
10.1038/embor.2008.146
Published
2008-10-00
Epub
2008-00-08
Pages
1013-8
Language
English
Region
England
NLM ID
100963049
PMCID
PMC2572124
Subset
IM
Grants
NCI NIH HHS · P01 CA016038 · United States
NIGMS NIH HHS · R01 GM026154 · United States
NIGMS NIH HHS · R01GM026154 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1038/embor.2008.146 PMC Full Text View journal details
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