Characterization of the mRNA capping apparatus of the microsporidian parasite Encephalitozoon cuniculi

被引:37
作者
Hausmann, S
Vivarès, CP
Shuman, S [1 ]
机构
[1] Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA
[2] Univ Clermont Ferrand, F-63177 Clermont Ferrand, France
关键词
D O I
10.1074/jbc.M109649200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A scheme of eukaryotic phylogeny has been suggested based on the structure and physical linkage of the enzymes that catalyze mRNA cap formation. Here we show that the intracellular parasite Encephatitozoon cuniculi encodes a complete mRNA capping apparatus consisting of separate triphosphatase (EcCet1), guanylyltransferase (EcCeg1), and methyltransferase (Ecm1) enzymes, which we characterize biochemically and genetically. The triphosphatase EcCetl belongs to a metal-dependent phosphohydrolase family that includes the triphosphatase components of the capping apparatus of fungi, DNA viruses, and the malaria parasite Plasmodium falciparum. These enzymes are structurally and mechanistically unrelated to the metal-independent cysteine phosphatase-type RNA tri-phosphatases found in metazoans and plants. Our findings support the proposed evolutionary connection between microsporidia and fungi, and they place fungi and protozoa in a common lineage distinct from that of metazoans and plants. RNA triphosphatase presents an attractive target for antiprotozoal/antifungal drug development.
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收藏
页码:96 / 103
页数:8
相关论文
共 35 条
[1]   Structure-function analysis of the active site tunnel of yeast RNA triphosphatase [J].
Bisaillon, M ;
Shuman, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) :17261-17266
[2]   mRNA: guanine-N7 cap methyltransferases: identification of novel members of the family, evolutionary analysis, homology modeling, and analysis of sequence-structure-function relationships [J].
Bujnicki, Janusz M. ;
Feder, Marcin ;
Radlinska, Monika ;
Rychlewski, Leszek .
BMC BIOINFORMATICS, 2001, 2 (1)
[3]   Structure and mechanism of the RNA triphosphatase component of mammalian mRNA capping enzyme [J].
Changela, A ;
Ho, CK ;
Martins, A ;
Shuman, S ;
Mondragón, A .
EMBO JOURNAL, 2001, 20 (10) :2575-2586
[4]   The highly reduced genome of an enslaved algal nucleus [J].
Douglas, S ;
Zauner, S ;
Fraunholz, M ;
Beaton, M ;
Penny, S ;
Deng, LT ;
Wu, XN ;
Reith, M ;
Cavalier-Smith, T ;
Maier, UG .
NATURE, 2001, 410 (6832) :1091-1096
[5]   X-ray crystallography reveals a large conformational change during guanyl transfer by mRNA capping enzymes [J].
Hakansson, K ;
Doherty, AJ ;
Shuman, S ;
Wigley, DB .
CELL, 1997, 89 (04) :545-553
[6]   An essential function of Saccharomyces cerevisiae RNA triphosphatase Cet1 is to stabilize RNA guanylyltransferase Ceg1 against thermal inactivation [J].
Hausmann, S ;
Ho, CK ;
Schwer, B ;
Shuman, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (39) :36116-36124
[7]   Microsporidia are related to Fungi: Evidence from the largest subunit of RNA polymerase II and other proteins [J].
Hirt, RP ;
Logsdon, JM ;
Healy, B ;
Dorey, MW ;
Doolittle, WF ;
Embley, TM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (02) :580-585
[8]   A yeast-like mRNA capping apparatus in Plasmodium falciparum [J].
Ho, CK ;
Shuman, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (06) :3050-3055
[9]   Yeast and viral RNA 5′ triphosphatases comprise a new nucleoside triphosphatase family [J].
Ho, CK ;
Pei, Y ;
Shuman, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (51) :34151-34156
[10]   RNA triphosphatase component of the mRNA capping apparatus of Paramecium bursaria Chlorella virus 1 [J].
Ho, CK ;
Gong, CL ;
Shuman, S .
JOURNAL OF VIROLOGY, 2001, 75 (04) :1744-1750