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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

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

Ruthrothaselvi Bharathavikru1, Tatiana Dudnakova2, Stuart Aitken1

  • 1Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.

Genes & Development
|March 15, 2017
PubMed

Insights

Wilms

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Wilms' tumor 1 (WT1) is crucial for mesodermal tissue development and homeostasis.
  • Evidence suggests WT1 has post-transcriptional functions, but its direct RNA targets were unknown.

Purpose of the Study:

  • To identify endogenous WT1 target RNAs.
  • To elucidate the mechanism of WT1-mediated gene regulation at the post-transcriptional level.

Main Methods:

  • RNA immunoprecipitation coupled with UV cross-linking (RIP-UV) to identify WT1-bound RNAs.
  • Cell culture and developing kidney mesenchyme models to study mRNA regulation.
  • Reporter gene assays to confirm WT1 interaction with 3' UTRs.

Main Results:

  • WT1 preferentially binds to the 3' untranslated regions (UTRs) of specific developmental target mRNAs.
  • WT1 depletion leads to decreased levels and increased turnover of these target mRNAs.
  • WT1 directly regulates gene expression via binding sites within 3' UTRs.

Conclusions:

  • WT1 regulates key developmental and disease processes by controlling mRNA turnover.
  • Identified direct RNA targets and binding mechanisms of WT1.
  • Highlights the importance of post-transcriptional regulation by WT1 in development.
Keywords:
3′ UTRFLASHRNA secondary structuresWT1developmental pathwayshybrids

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