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Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast |
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| Authors: | Lo Chor-Wai Kaida Daisuke Nishimura Shinichi Matsuyama Akihisa Yashiroda Yoko Taoka Hiroshi Ishigami Ken Watanabe Hidenori Nakajima Hidenori Tani Tokio Horinouchi Sueharu Yoshida Minoru |
| Institution: | a Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan b Department of Biotechnology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan c Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan d Drug Discovery Research, Fermentation Research Laboratories, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan e Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555, Japan f Japan Science and Technology Corporation (JST), CREST Research Project, Kawaguchi, Saitama 332-0012, Japan |
| 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. |
| Keywords: | Spliceostatin A Fission yeast Pre-mRNA SF3b Splicing Pre-mRNA retention |
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