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Spliceostatin A stabilizes CDKN1B mRNA through the 3' UTR

Daisuke Kaida1, Kenta Shida1

  • 1Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Biochemical and Biophysical Research Communications
|April 5, 2022
PubMed

Insights

Spliceostatin A (SSA) upregulates p27 protein by stabilizing CDKN1B mRNA, not affecting transcription. The 3' untranslated region of CDKN1B mRNA is key to this post-transcriptional regulation.

Area of Science:

  • Molecular Biology
  • Gene Expression Regulation
  • Cell Cycle Control

Background:

  • Pre-mRNA splicing is crucial for eukaryotic gene expression; splicing inhibitors impact cellular functions.
  • Spliceostatin A (SSA), a potent splicing inhibitor, induces cell cycle arrest at G1 and G2/M phases.
  • SSA treatment leads to p27 protein upregulation, contributing to G1 phase arrest, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism behind p27 protein upregulation induced by SSA.
  • To investigate the effect of SSA on CDKN1B gene expression at transcriptional and post-transcriptional levels.
  • To identify the specific mRNA regions involved in SSA-mediated regulation.

Main Methods:

  • Analysis of p27 protein levels and CDKN1B mRNA expression following SSA treatment.
  • Assessment of CDKN1B gene transcription rates.
  • Investigation of mRNA stability, focusing on the 3' untranslated region (3' UTR).

Main Results:

  • SSA treatment resulted in p27 protein stabilization and increased CDKN1B mRNA levels.
  • SSA did not alter CDKN1B gene transcription but enhanced CDKN1B mRNA stability.
  • The 3' UTR of CDKN1B mRNA was identified as a critical element in SSA-induced mRNA stabilization.

Conclusions:

  • SSA upregulates p27 protein primarily through the stabilization of CDKN1B mRNA.
  • This post-transcriptional regulation mechanism involves the 3' untranslated region of CDKN1B mRNA.
  • Understanding this pathway provides insights into splicing inhibitor effects on gene expression and cell cycle control.
Keywords:
CDKN1BSpliceostatin ASplicingUTRp27

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