A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins

被引:444
作者
Ishizuka, A
Siomi, MC
Siomi, H [1 ]
机构
[1] Univ Tokushima, Inst Genome Res, Tokushima 7708503, Japan
[2] Univ Tokushima, Grad Sch Nutr, Tokushima 7708503, Japan
关键词
fragile x syndrome; FMR1; RNAi; RNA helicase; miRNA;
D O I
10.1101/gad.1022002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Fragile X syndrome is a common form of inherited mental retardation caused by the loss of FMR1 expression. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. In Drosophila, the fly homolog of the FMR1 protein (dFMR1) binds to and represses the translation of an mRNA encoding of the microtuble-associated protein Futsch. We have isolated a dFMRl -associated complex that includes two ribosomal proteins, L5 and L11, along with 5S RNA. The dFMR1 complex also contains Argonaute2 (AG02) and a Drosophila homolog of p68 RNA helicase (Dmp68). AGO2 is an essential component for the RNA-induced silencing complex (RISC), a sequence-specific nuclease complex that mediates RNA interference (RNAi) in Drosophila. We show that Dmp68 is also required for efficient RNAL We further show that dFMR1 is associated with Dicer, another essential component of the RNAi pathway, and microRNAs (miRNAs) in vivo, suggesting that dFMR1 is part of the RNAi-related apparatus. Our findings suggest a model in which the RNAi and dFMR1-mediated translational control pathways intersect in Drosophila. Our findings also raise the possibility that defects in an RNAi-related machinery may cause human disease.
引用
收藏
页码:2497 / 2508
页数:12
相关论文
共 81 条
[61]   Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation [J].
Seggerson, K ;
Tang, LJ ;
Moss, EG .
DEVELOPMENTAL BIOLOGY, 2002, 243 (02) :215-225
[62]   RNA-binding proteins as regulators of gene expression [J].
Siomi, H ;
Dreyfuss, G .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1997, 7 (03) :345-353
[63]   THE PROTEIN PRODUCT OF THE FRAGILE-X GENE, FMR1, HAS CHARACTERISTICS OF AN RNA-BINDING PROTEIN [J].
SIOMI, H ;
SIOMI, MC ;
NUSSBAUM, RL ;
DREYFUSS, G .
CELL, 1993, 74 (02) :291-298
[64]  
Siomi MC, 1996, MOL CELL BIOL, V16, P3825
[65]   A 5S RIBOSOMAL-RNA L5 COMPLEX IS A PRECURSOR TO RIBOSOME ASSEMBLY IN MAMMALIAN-CELLS [J].
STEITZ, JA ;
BERG, C ;
HENDRICK, JP ;
LABRANCHECHABOT, H ;
METSPALU, A ;
RINKE, J ;
YARIO, T .
JOURNAL OF CELL BIOLOGY, 1988, 106 (03) :545-556
[66]  
Stevenson RJ, 1998, J PATHOL, V184, P351, DOI 10.1002/(SICI)1096-9896(199804)184:4<351::AID-PATH1235>3.0.CO
[67]  
2-C
[68]   5S ribosomal RNA database Y2K [J].
Szymanski, M ;
Barciszewska, MZ ;
Barciszewski, J ;
Erdmann, VA .
NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :166-167
[69]   The rde-1 gene, RNA interference, and transposon silencing in C-elegans [J].
Tabara, H ;
Sarkissian, M ;
Kelly, WG ;
Fleenor, J ;
Grishok, A ;
Timmons, L ;
Fire, A ;
Mello, CC .
CELL, 1999, 99 (02) :123-132
[70]   The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExX-box helicase to direct RNAi in C-elegans [J].
Tabara, H ;
Yigit, E ;
Siomi, H ;
Mello, CC .
CELL, 2002, 109 (07) :861-871