論文

査読有り 国際誌
2017年1月

Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A.

RNA (New York, N.Y.)
  • Rei Yoshimoto
  • ,
  • Daisuke Kaida
  • ,
  • Masaaki Furuno
  • ,
  • A Maxwell Burroughs
  • ,
  • Shohei Noma
  • ,
  • Harukazu Suzuki
  • ,
  • Yumi Kawamura
  • ,
  • Yoshihide Hayashizaki
  • ,
  • Akila Mayeda
  • ,
  • Minoru Yoshida

23
1
開始ページ
47
終了ページ
57
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1261/rna.058065.116
出版者・発行元
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT

Spliceostatin A (SSA) is a methyl ketal derivative of FR901464, a potent antitumor compound isolated from a culture broth of Pseudomonas sp no. 2663. These compounds selectively bind to the essential spliceosome component SF3b, a subcomplex of the U2 snRNP, to inhibit pre-mRNA splicing. However, the mechanism of SSA's antitumor activity is unknown. It is noteworthy that SSA causes accumulation of a truncated form of the CDK inhibitor protein p27 translated from CDKN1B pre-mRNA, which is involved in SSA-induced cell-cycle arrest. However, it is still unclear whether pre-mRNAs are uniformly exported from the nucleus following SSA treatment. We performed RNA-seq analysis on nuclear and cytoplasmic fractions of SSA-treated cells. Our statistical analyses showed that intron retention is the major consequence of SSA treatment, and a small number of intron-containing pre-mRNAs leak into the cytoplasm. Using a series of reporter plasmids to investigate the roles of intronic sequences in the pre-mRNA leakage, we showed that the strength of the 5' splice site affects pre-mRNA leakage. Additionally, we found that the level of pre-mRNA leakage is related to transcript length. These results suggest that the strength of the 5' splice site and the length of the transcripts are determinants of the pre-mRNA leakage induced by SF3b inhibitors.

リンク情報
DOI
https://doi.org/10.1261/rna.058065.116
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27754875
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159648
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000391687100006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1261/rna.058065.116
  • ISSN : 1355-8382
  • eISSN : 1469-9001
  • PubMed ID : 27754875
  • PubMed Central 記事ID : PMC5159648
  • Web of Science ID : WOS:000391687100006

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