A U2-snRNP–independent role of SF3b in promoting mRNA export

  • Ke Wang
  • , Changping Yin
  • , Xian Du
  • , Suli Chen
  • , Jianshu Wang
  • , Li Zhang
  • , Lantian Wang
  • , Yong Yu
  • , Binkai Chi
  • , Min Shi
  • , Changshou Wang
  • , Robin Reed
  • , Yu Zhou
  • , Jing Huang
  • , Hong Cheng

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

To ensure efficient and accurate gene expression, pre-mRNA processing and mRNA export need to be balanced. However, how this balance is ensured remains largely unclear. Here, we found that SF3b, a component of U2 snRNP that participates in splicing and 3′ processing of pre-mRNAs, interacts with the key mRNA export adaptor THO in vivo and in vitro. Depletion of SF3b reduces THO binding with the mRNA and causes nuclear mRNA retention. Consistently, introducing SF3b binding sites into the mRNA enhances THO recruitment and nuclear export in a dose-dependent manner. These data demonstrate a role of SF3b in promoting mRNA export. In support of this role, SF3b binds with mature mRNAs in the cells. Intriguingly, disruption of U2 snRNP by using a U2 antisense morpholino oligonucleotide does not inhibit, but promotes, the role of SF3b in mRNA export as a result of enhanced SF3b–THO interaction and THO recruitment to the mRNA. Together, our study uncovers a U2-snRNP–independent role of SF3b in mRNA export and suggests that SF3b contributes to balancing pre-mRNA processing and mRNA export.

Original languageEnglish
Pages (from-to)7837-7846
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number16
DOIs
StatePublished - 16 Apr 2019
Externally publishedYes

Keywords

  • MRNA export
  • Pre-mRNA processing
  • SF3b
  • THO
  • U2 snRNP

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