Spliceostatin A interaction with SF3B limits U1 snRNP availability and causes premature cleavage and polyadenylation

Rei Yoshimoto, Jagat K. Chhipi-Shrestha, Tilman Schneider-Poetsch, Masaaki Furuno, A. Maxwell Burroughs, Shohei Noma, Harukazu Suzuki, Yoshihide Hayashizaki, Akila Mayeda, Shinichi Nakagawa, Daisuke Kaida, Shintaro Iwasaki, Minoru Yoshida

Research output: Contribution to journalArticlepeer-review

Abstract

RNA splicing, a highly conserved process in eukaryotic gene expression, is seen as a promising target for anticancer agents. Splicing is associated with other RNA processing steps, such as transcription and nuclear export; however, our understanding of the interaction between splicing and other RNA regulatory mechanisms remains incomplete. Moreover, the impact of chemical splicing inhibition on long non-coding RNAs (lncRNAs) has been poorly understood. Here, we demonstrate that spliceostatin A (SSA), a chemical splicing modulator that binds to the SF3B subcomplex of the U2 small nuclear ribonucleoprotein particle (snRNP), limits U1 snRNP availability in splicing, resulting in premature cleavage and polyadenylation of MALAT1, a nuclear lncRNA, as well as protein-coding mRNAs. Therefore, truncated transcripts are exported into the cytoplasm and translated, resulting in aberrant protein products. Our work demonstrates that active recycling of the splicing machinery maintains homeostasis of RNA processing beyond intron excision.

Original languageEnglish
JournalCell Chemical Biology
DOIs
Publication statusAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Fingerprint

Dive into the research topics of 'Spliceostatin A interaction with SF3B limits U1 snRNP availability and causes premature cleavage and polyadenylation'. Together they form a unique fingerprint.

Cite this