Transcription factor Wilms' tumor 1 regulates developmental RNAs through 3′ UTR interaction

被引：35

作者：

Bharathavikru, Ruthrothaselvi ^{[1
]}

Dudnakova, Tatiana ^{[2
]}

Aitken, Stuart ^{[1
]}

Slight, Joan ^{[1
]}

Artibani, Mara ^{[1
,4
]}

Hohenstein, Peter ^{[1
,3
]}

Tollervey, David ^{[2
]}

Hastie, Nick ^{[1
]}

机构：

[1] Univ Edinburgh, Western Gen Hosp, MRC, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3BF, Midlothian, Scotland

[3] Univ Edinburgh, Roslin Inst, Easter Bush EH25 9RG, Midlothian, Scotland

[4] Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England

来源：

GENES & DEVELOPMENT | 2017年 / 31卷 / 04期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

WT1; FLASH; 3 ' UTR; hybrids; RNA secondary structures; developmental pathways; PROTEIN WT1; GENE; EXPRESSION; REVEALS; BINDING; MUTATIONS; MECHANISMS; DOMAINS; SEX;

D O I：

10.1101/gad.291500.116

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Wilms' tumor 1 (WT1) is essential for the development and homeostasis of multiple mesodermal tissues. Despite evidence for post-transcriptional roles, no endogenous WT1 target RNAs exist. Using RNA immunoprecipitation and UV cross-linking, we show that WT1 binds preferentially to 3' untranslated regions (UTRs) of developmental targets. These target mRNAs are down-regulated upon WT1 depletion in cell culture and developing kidney mesenchyme. Wt1 deletion leads to rapid turnover of specific mRNAs. WT1 regulates reporter gene expression through interaction with 3' UTR-binding sites. Combining experimental and computational analyses, we propose that WT1 influences key developmental and disease processes in part through regulating mRNA turnover.

引用

页码：347 / 352

页数：6

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