RNA EDITING IN THE WILMS-TUMOR SUSCEPTIBILITY GENE, WT1
RNA EDITING IN THE WILMS-TUMOR SUSCEPTIBILITY GENE, WT1
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DOI：
10.1101/gad.8.6.720
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发表时间：
1994-03-15
影响因子：
10.5
通讯作者：
SUKUMAR, S
中科院分区：
文献类型：
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作者：
SHARMA, PM;BOWMAN, M;SUKUMAR, S
大鼠肾脏WT1cDNA在839位含有胸苷或胞嘧啶残基。WT1基因组DNA仅含T839。为了解释这些结果，我们认为WT1转录本经历了RNA编辑，其中U839被转换为C，导致WT1中的亮氨酸280被Pro取代。在来自人睾丸的WT1cDNAs中观察到了相同核苷酸的RNA编辑。在功能测试中，WT1-亮氨酸280多肽在体外测试中抑制EGR-1启动子的效率比WT1-Pro高约30%。编辑后的WT1-C839mRNA在新生大鼠肾脏中几乎检测不到，而成年大鼠肾脏中同时含有U839和C839-WT1mRNA，提示这两种蛋白亚型在生长和分化中起作用。
Rat kidney WT1 cDNAs contain either a thymidine or a cytosine residue at position 839. Genomic WT1 DNA contains only T839. To explain these results, we propose the WT1 transcript undergoes RNA editing in which U839 is converted to C, resulting in the replacement of leucine 280 in WT1 by proline. RNA editing at the same nucleotide was observed in WT1 cDNAs from human testis. In functional assays, the WT1-leucine280 polypeptide repressed the EGR-1 promoter in in vitro assays approximately 30% more efficiently than WT1-proline. Edited WT1-C839 mRNA was barely detectable in neonatal kidney, whereas adult rat kidneys contained both U839 and C839-WT1 mRNA, suggesting a role for the two protein isoforms in growth and differentiation.