Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast.
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.
Lo
Chor-Wai
CW
Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Kaida
Daisuke
D
Nishimura
Shinichi
S
Matsuyama
Akihisa
A
Yashiroda
Yoko
Y
Taoka
Hiroshi
H
Ishigami
Ken
K
Watanabe
Hidenori
H
Nakajima
Hidenori
H
Tani
Tokio
T
Horinouchi
Sueharu
S
Yoshida
Minoru
M
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*
D005656:Fungal Proteins; D012322:RNA Precursors