Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast

Chor Wai Lo, Daisuke Kaida, Shinichi Nishimura, Akihisa Matsuyama, Yoko Yashiroda, Hiroshi Taoka, Ken Ishigami, Hidenori Watanabe, Hidenori Nakajima, Tokio Tani, Sueharu Horinouchi, Minoru Yoshida*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Nuclear retention of pre-mRNAs is tightly regulated by several security mechanisms that prevent pre-mRNA export into the cytoplasm. Recently, spliceostatin A, a methylated derivative of a potent antitumor microbial metabolite FR901464, was found to cause pre-mRNA accumulation and translation in mammalian cells. Here we report that spliceostatin A also inhibits splicing and nuclear retention of pre-mRNA in a fission yeast strain that lacks the multidrug resistance protein Pmd1. As observed in mammalian cells, spliceostatin A is bound to components of the SF3b complex in the spliceosome. Furthermore, overexpression of nup211, a homolog of Saccharomyces cerevisiae MLP1, suppresses translation of pre-mRNAs accumulated by spliceostatin A. These results suggest that the SF3b complex has a conserved role in pre-mRNA retention, which is independent of the Mlp1 function.

Original languageEnglish
Pages (from-to)573-577
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume364
Issue number3
DOIs
StatePublished - 2007/12/21

Keywords

  • Fission yeast
  • Pre-mRNA
  • Pre-mRNA retention
  • SF3b
  • Spliceostatin A
  • Splicing

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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