PIN domain of Nob1p is required for D-site cleavage in 20S pre-rRNA

被引：104
作者：
Fatica, A
Tollervey, D
Dlakic, M
机构：
[1] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA
[2] Univ Roma La Sapienza, Dipartimento Genet & Biol Mol, I-00185 Rome, Italy
[3] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland
来源：
RNA | 2004年 / 10卷 / 11期
关键词：
rRNA processing; ribosome synthesis; endonuclease; homology modeling;
D O I：
10.1261/rna.7123504
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：
Nob1p (Yor056c) is essential for processing of the 20S pre-rRNA to the mature 18S rRNA. It is part of a pre-40S ribosomal particle that is transported to the cytoplasm and subsequently cleaved at the 3' end of mature 18S rRNA (D-site). Nob1p is also reported to participate in proteasome biogenesis, and it was therefore unclear whether its primary activity is in ribosome synthesis. In this work, we describe a homology model of the PIN domain of Nob1p, which structurally Mimics Mg2+-dependent exonucleases despite negligible similarity in primary sequence. Insights gained from this model were used to design a point mutation that was predicted to abolish the postulated enzymatic activity. Cells expressing Nob1p with this mutation failed to cleave the 20S pre-rRNA. This supports both the significance of the structural model and the idea that Nob1p is the long-sought D-site endonuclease.
引用
收藏
页码：1698 / 1701
页数：4
相关论文
共 37 条
[1]   Distant structural homology leads to the functional characterization of an archaeal PIN domain as an exonuclease [J].
Arcus, VL ;
Bäckbro, K ;
Roos, A ;
Daniel, EL ;
Baker, EN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (16) :16471-16478
[2]   IDENTIFICATION OF RESIDUES IN THE MU-TRANSPOSASE ESSENTIAL FOR CATALYSIS [J].
BAKER, TA ;
LUO, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (14) :6654-6658
[3]   Identification of a 60S preribosomal particle that is closely linked to nuclear export [J].
Bassler, J ;
Grandi, P ;
Gadal, O ;
Lessmann, T ;
Petfalski, E ;
Tollervey, D ;
Lechner, J ;
Hurt, E .
MOLECULAR CELL, 2001, 8 (03) :517-529
[4]   PIN domains in nonsense-mediated mRNA decay and RNAi [J].
Clissold, PM ;
Ponting, CP .
CURRENT BIOLOGY, 2000, 10 (24) :R888-R890
[5]   The Noc proteins involved in ribosome synthesis and export contain divergent HEAT repeats [J].
Dlakic, M ;
Tollervey, D .
RNA, 2004, 10 (03) :351-354
[6]   A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis [J].
Dragon, F ;
Gallagher, JEG ;
Compagnone-Post, PA ;
Mitchell, BM ;
Porwancher, KA ;
Wehner, KA ;
Wormsley, S ;
Settlage, RE ;
Shabanowitz, J ;
Osheim, Y ;
Beyer, AL ;
Hunt, DF ;
Baserga, SJ .
NATURE, 2002, 417 (6892) :967-970
[7]   Yph1p, an ORC-interacting protein: Potential links between cell proliferation control, DNA replication, and ribosome biogenesis [J].
Du, YCN ;
Stillman, B .
CELL, 2002, 109 (07) :835-848
[8]   Cic1p/Nsa3p is required for synthesis and nuclear export of 60S ribosomal subunits [J].
Fatica, A ;
Oeffinger, M ;
Tollervey, D ;
Bozzoni, I .
RNA, 2003, 9 (12) :1431-1436
[9]   Nob1p is required for cleavage of the 3′ end of 18S rRNA [J].
Fatica, A ;
Oeffinger, M ;
Dlakic, M ;
Tollervey, D .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (05) :1798-1807
[10]   Making ribosomes [J].
Fatica, A ;
Tollervey, D .
CURRENT OPINION IN CELL BIOLOGY, 2002, 14 (03) :313-318
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