title: Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast.
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.
authors.affiliation: Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Chor-Wai
authors.initials: CW
authors.lastname: Lo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kaida
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimura
authors.forename: Akihisa
authors.initials: A
authors.lastname: Matsuyama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yashiroda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Taoka
authors.forename: Ken
authors.initials: K
authors.lastname: Ishigami
authors.forename: Hidenori
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nakajima
authors.forename: Tokio
authors.initials: T
authors.lastname: Tani
authors.forename: Sueharu
authors.initials: S
authors.lastname: Horinouchi
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D002467:Cell Nucleus / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D012440:Saccharomyces / Q000235:genetics*; D017381:Spliceosomes / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D012322:RNA Precursors