An RNA recognition motif in Wilms' tumour protein (WT1) revealed by structural modelling

被引:96
作者
Kennedy, D
Ramsdale, T
Mattick, JS
Little, M
机构
[1] UNIV QUEENSLAND, CTR CELLULAR & MOLEC BIOL, BRISBANE, QLD 4072, AUSTRALIA
[2] UNIV QUEENSLAND, DEPT BIOCHEM, ST LUCIA, QLD 4072, AUSTRALIA
[3] UNIV QUEENSLAND, CTR DRUG DESIGN & DEV, ST LUCIA, QLD 4072, AUSTRALIA
关键词
D O I
10.1038/ng0396-329
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The Wilms' tumour suppressor gene 1 (WT1) encodes four C2H2 zinc finger- containing proteins critical for normal mammalian urogenital development. Mutations in this gene are observed in the childhood kidney cancer, Wilms' tumour (WT). WT1 can bind specific DNA targets within the promoters of many genes and both transcriptional repression and activation domains have been identified. On this basis, it has been assumed that regulation of transcription is the basis of WT1 tumour suppressor activity. However, subnuclear localization studies have revealed an association between WT1 proteins and 'speckled bodies' within the nucleus. Degradation of nuclear RNA in cells expressing WT1 abolishes this speckled localization and WT1 co- immunoprecipitates with a number of spliceosomal proteins, suggesting that it may also bind to RNA. Using structural rather than sequence comparison, we have now identified an evolutionarily conserved N-terminal RNA recognition motif (RRM) in all known WT1 isoforms similar to that in the constitutive splicing factor U1A. Given the association between WT1 mutations and Wilms' tumours, this study, together with ether recent findings, may suggest a novel tumour suppression mechanism.
引用
收藏
页码:329 / 332
页数:4
相关论文
共 29 条
[21]   ASSESSMENT OF PROTEIN MODELS WITH 3-DIMENSIONAL PROFILES [J].
LUTHY, R ;
BOWIE, JU ;
EISENBERG, D .
NATURE, 1992, 356 (6364) :83-85
[22]   CRYSTAL-STRUCTURE OF THE RNA-BINDING DOMAIN OF THE U1 SMALL NUCLEAR RIBONUCLEOPROTEIN-A [J].
NAGAI, K ;
OUBRIDGE, C ;
JESSEN, TH ;
LI, J ;
EVANS, PR .
NATURE, 1990, 348 (6301) :515-520
[23]  
NAKAGAMA H, 1995, MOL CELL BIOL, V15, P1489
[24]   CRYSTAL-STRUCTURE AT 1.92 ANGSTROM RESOLUTION OF THE RNA-BINDING DOMAIN OF THE U1A SPLICEOSOMAL PROTEIN COMPLEXED WITH AN RNA HAIRPIN [J].
OUBRIDGE, C ;
ITO, N ;
EVANS, PR ;
TEO, CH ;
NAGAI, K .
NATURE, 1994, 372 (6505) :432-438
[25]   BINDING OF THE WILMS-TUMOR LOCUS ZINC FINGER PROTEIN TO THE EGR-1 CONSENSUS SEQUENCE [J].
RAUSCHER, FJ ;
MORRIS, JF ;
TOURNAY, OE ;
COOK, DM ;
CURRAN, T .
SCIENCE, 1990, 250 (4985) :1259-1262
[26]   THE WT1 WILMS-TUMOR GENE-PRODUCT - A DEVELOPMENTALLY-REGULATED TRANSCRIPTION FACTOR IN THE KIDNEY THAT FUNCTIONS AS A TUMOR-SUPPRESSOR [J].
RAUSCHER, FJ .
FASEB JOURNAL, 1993, 7 (10) :896-903
[27]   WT1-MEDIATED TRANSCRIPTIONAL ACTIVATION IS INHIBITED BY DOMINANT-NEGATIVE MUTANT PROTEINS [J].
REDDY, JC ;
MORRIS, JC ;
WANG, J ;
ENGLISH, MA ;
HABER, DA ;
SHI, Y ;
LICHT, JD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (18) :10878-10884
[28]  
SMITH CWJ, 1989, ANNU REV GENET, V23, P527, DOI 10.1146/annurev.ge.23.120189.002523
[29]  
WANG ZY, 1993, J BIOL CHEM, V268, P9172