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Enhancers regulate 3' end processing activity to control expression of alternative 3'UTR isoforms.

Buki Kwon1, Mervin M Fansler1,2, Neil D Patel1

  • 1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

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|May 17, 2022
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Summary
This summary is machine-generated.

Transcriptional enhancers regulate alternative 3' untranslated region (UTR) isoform expression in a cell type-specific manner. Enhancers control 3' end processing activity, influencing which 3'UTR isoform is produced.

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Transcriptomics

Background:

  • Alternative 3' untranslated region (UTR) isoforms are expressed in a cell type-specific manner.
  • Transcriptional enhancers are known regulators of mRNA expression levels.

Purpose of the Study:

  • To investigate whether transcriptional enhancers regulate 3'UTR isoform expression.
  • To elucidate the mechanism by which enhancers influence 3'UTR isoform selection.

Main Methods:

  • Endogenous enhancer deletion in the PTEN gene.
  • Silencing of enhancer-bound transcription factors.
  • Reporter assays with single- and multi-UTR gene promoters.
  • Analysis of polyadenylation site processing activity.

Main Results:

  • Enhancer deletion in PTEN prevented 3'UTR isoform switching without affecting overall transcript production.
  • Silencing an enhancer-bound transcription factor recapitulated the effect of enhancer deletion.
  • Enhancers increased 3' end processing activity at polyadenylation sites when paired with multi-UTR gene promoters.

Conclusions:

  • Transcriptional enhancers play a crucial role in regulating cell type- and condition-specific 3'UTR isoform expression.
  • Enhancers integrate cellular signals to modulate alternative polyadenylation and 3'UTR selection.
  • This mechanism allows for fine-tuning of gene expression beyond transcript levels.