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

Genes Dev. 2017 Feb 15;31(4):347-352. doi: 10.1101/gad.291500.116. Epub 2017 Mar 13.

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.

Keywords: 3′ UTR; FLASH; RNA secondary structures; WT1; developmental pathways; hybrids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / physiology*
  • Animals
  • Cell Line
  • Down-Regulation
  • Gene Deletion
  • Gene Expression Regulation, Developmental / genetics*
  • Kidney / cytology
  • Mesoderm / metabolism
  • Mice
  • Mouse Embryonic Stem Cells
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Wilms Tumor / genetics*
  • Wilms Tumor / metabolism*

Substances

  • 3' Untranslated Regions
  • RNA, Messenger