A new activity provided by a chemical splicing modulator is discovered

March 30, 2021

Revealing the mechanism of a strong anticancer activity of spliceostatin A (SSA)

A cooperative research group of RIKEN Center for Sustainable Resource Science, Cluster for Pioneering Research and Center for Integrative Medical Sciences has discovered that a chemical splicing modulator, spliceostatin A (SSA), induces premature cleavage and polyadenylation (addition of a sequence of multiple adenosines) in RNAs in cells.

SSA binds to SF3b subcomplex necessary for splicing to inhibits splicing, leading to the accumulation of precursor messenger RNAs (mRNA).
In the present study, the group conducted transcriptome analysis and revealed that, in addition to inhibiting splicing, SSA produces premature cleavage and polyadenylation in "MALAT1", a long noncoding RNA, and some other mRNAs.

The findings of this study will help elucidate functional mechanisms of chemical splicing modulators including SSA having anticancer activities and new functions of non-coding RNAs.

Original article
Cell Chemical Biology doi:10.1016/j.chembiol.2021.03.002
R. Yoshimoto, J. K. Chhipi-Shrestha, T. Schneider-Poetsch, M. Furuno, A. M. Burroughs, S. Noma, H. Suzuki, Y. Hayashizaki, A. Mayeda, S. Nakagawa, D. Kaida, S. Iwasaki, M. Yoshida,
"Spliceostatin A interaction with SF3B1 limits U1 snRNP availability and causes premature cleavage and polyadenylation".
Minoru Yoshida
Group Director
Chemical Genomics Research Group