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

ABSTRACT: 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.

SUBMITTER: Bharathavikru R

PROVIDER: S-EPMC5358755 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Bharathavikru Ruthrothaselvi R Dudnakova Tatiana T Aitken Stuart S Slight Joan J Artibani Mara M Hohenstein Peter P Tollervey David D Hastie Nick N

Genes & development 20170201 4

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. <i>Wt1</i> deletion leads to rapid turnover of specific ...[more]

PMID: 28289143

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