RNA binding by the Wilms tumor suppressor zinc finger proteins.
The Wilms tumor suppressor gene WT1 is implicated in the ontogeny of genito-urinary abnormalities, including Denys-Drash syndrome and Wilms tumor of the kidney. WT1 encodes Kruppel-type zinc finger proteins that can regulate the expression of several growth-related genes, apparently by binding to specific DNA sites located within 5' untranslated leader regions as well as 5' promoter sequences. Both WT1 and a closely related early growth response factor, EGR1, can bind the same DNA sequences from the mouse gene encoding insulin-like growth factor 2 (Igf-2). We report that WT1, but not EGR1, can bind specific Igf-2 exonic RNA sequences, and that the zinc fingers are required for this interaction. WT1 zinc finger 1, which is not represented in EGR1, plays a more significant role in RNA binding than zinc finger 4, which does have a counterpart in EGR1. Furthermore, the normal subnuclear localization of WT1 proteins is shown to be RNase, but not DNase, sensitive. Therefore, WT1 might, like the Kruppel-type zinc finger protein TFIIIA, regulate gene expression by both transcriptional and posttranscriptional mechanisms.
Caricasole
A
A
Cancer Research Campaign Growth Factors, Department of Zoology, University of Oxford, United Kingdom.
Duarte
A
A
Larsson
S H
SH
Hastie
N D
ND
Little
M
M
Holmes
G
G
Todorov
I
I
Ward
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002880:Chromosomes, Human, Pair 11; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D005091:Exons; D016162:Genes, Wilms Tumor; D006801:Humans; D017874:Immediate-Early Proteins; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013577:Syndrome; D014157:Transcription Factors / Q000378:metabolism*; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D012313:RNA; D007335:Insulin-Like Growth Factor II