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Crystal structure of the 25 kDa subunit of human cleavage factor Im.

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Coseno M, Martin G, Berger C, Gilmartin G, Keller W, Doublié S
OpenAccess logo Nucleic Acids Res 36 3474-83 (2008)
Cited: 31 times
EuropePMC logo PMID: 18445629

Abstract

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.

Reviews - 3bap mentioned but not cited (2)

  1. Delineating the structural blueprint of the pre-mRNA 3'-end processing machinery. Xiang K, Tong L, Manley JL. Mol Cell Biol 34 1894-1910 (2014)
  2. Structural biology of poly(A) site definition. Yang Q, Doublié S. Wiley Interdiscip Rev RNA 2 732-747 (2011)

Articles - 3bap mentioned but not cited (4)



Reviews citing this publication (7)

  1. Pre-mRNA 3'-end processing complex assembly and function. Chan S, Choi EA, Shi Y. Wiley Interdiscip Rev RNA 2 321-335 (2011)
  2. The structure of human cleavage factor I(m) hints at functions beyond UGUA-specific RNA binding: a role in alternative polyadenylation and a potential link to 5' capping and splicing. Yang Q, Gilmartin GM, Doublié S. RNA Biol 8 748-753 (2011)
  3. Alternative polyadenylation of mRNA and its role in cancer. Yuan F, Hankey W, Wagner EJ, Li W, Wang Q. Genes Dis 8 61-72 (2021)
  4. Re-evaluation of Diadenosine Tetraphosphate (Ap4A) From a Stress Metabolite to Bona Fide Secondary Messenger. Ferguson F, McLennan AG, Urbaniak MD, Jones NJ, Copeland NA. Front Mol Biosci 7 606807 (2020)
  5. Deciphering molecular mechanisms of mRNA metabolism in the deep-branching eukaryote Entamoeba histolytica. López-Camarillo C, López-Rosas I, Ospina-Villa JD, Marchat LA. Wiley Interdiscip Rev RNA 5 247-262 (2014)
  6. Targeting the Polyadenylation Signal of Pre-mRNA: A New Gene Silencing Approach for Facioscapulohumeral Dystrophy. Marsollier AC, Joubert R, Mariot V, Dumonceaux J. Int J Mol Sci 19 E1347 (2018)
  7. mRNA 3' end processing and more--multiple functions of mammalian cleavage factor I-68. Ruepp MD, Schümperli D, Barabino SM. Wiley Interdiscip Rev RNA 2 79-91 (2011)

Articles citing this publication (18)



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