Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3' Splice Site Selection through Use of a Different Branch Point Academic Article uri icon


MeSH Major

  • Alternative Splicing
  • Mutation
  • Neoplasms
  • Phosphoproteins
  • Ribonucleoprotein, U2 Small Nuclear


  • Recurrent mutations in the spliceosome are observed in several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, the most frequently mutated component of the spliceosome in cancer, is involved in the recognition of the branch point sequence (BPS) during selection of the 3' splice site (ss) in RNA splicing. Here, we report that common and tumor-specific splicing aberrations are induced by SF3B1 mutations and establish aberrant 3' ss selection as the most frequent splicing defect. Strikingly, mutant SF3B1 utilizes a BPS that differs from that used by wild-type SF3B1 and requires the canonical 3' ss to enable aberrant splicing during the second step. Approximately 50% of the aberrantly spliced mRNAs are subjected to nonsense-mediated decay resulting in downregulation of gene and protein expression. These findings ascribe functional significance to the consequences of SF3B1 mutations in cancer.


publication date

  • January 2015



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2015.09.053

PubMed ID

  • 26565915

Additional Document Info

start page

  • 1033

end page

  • 45


  • 13


  • 5