Spliceostatin A stabilizes CDKN1B mRNA through the 3' UTR

Biochem Biophys Res Commun. 2022 Jun 11:608:39-44. doi: 10.1016/j.bbrc.2022.03.085. Epub 2022 Mar 29.

Abstract

Pre-mRNA splicing is one of the most important mechanisms in gene expression in eukaryotes, and therefore splicing inhibition affects various cellular functions. We previously reported that the potent splicing inhibitor spliceostatin A (SSA) causes cell cycle arrest at G1 and G2/M phases. Upregulation of the p27 cyclin dependent kinase inhibitor, encoded by the CDKN1B gene, is one of the reasons for G1 phase arrest caused by SSA treatment. However, the molecular mechanism of p27 upregulation by SSA remains unknown. In this study, we found that SSA treatment caused stabilization of the p27 protein and increase of CDKN1B mRNA. SSA did not affect transcription of CDKN1B gene, but stabilized CDKN1B mRNA. Finally, we revealed that the 3' untranslated region of CDKN1B mRNA was involved in the stabilization. These results suggest that stabilization of CDKN1B mRNA is one of the reasons of upregulation of the p27 protein by SSA.

Keywords: CDKN1B; Spliceostatin A; Splicing; UTR; p27.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Pyrans* / pharmacology
  • RNA, Messenger / genetics
  • Spiro Compounds* / pharmacology

Substances

  • 3' Untranslated Regions
  • Pyrans
  • RNA, Messenger
  • Spiro Compounds
  • spliceostatin A
  • Cyclin-Dependent Kinase Inhibitor p27