Progression through the spliceosome cycle requires Prp38p function for U4/U6 snRNA dissociation

EMBO J. 1998 May 15;17(10):2938-46. doi: 10.1093/emboj/17.10.2938.


The elaborate and energy-intensive spliceosome assembly pathway belies the seemingly simple chemistry of pre-mRNA splicing. Prp38p was previously identified as a protein required in vivo and in vitro for the first pre-mRNA cleavage reaction catalyzed by the spliceosome. Here we show that Prp38p is a unique component of the U4/U6.U5 tri-small nuclear ribonucleoprotein (snRNP) particle and is necessary for an essential step late in spliceosome maturation. Without Prp38p activity spliceosomes form, but arrest in a catalytically impaired state. Functional spliceosomes shed U4 snRNA before 5' splice-site cleavage. In contrast, Prp38p-defective spliceosomes retain U4 snRNA bound to its U6 snRNA base-pairing partner. Prp38p is the first tri-snRNP-specific protein shown to be dispensable for assembly, but required for conformational changes which lead to catalytic activation of the spliceosome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • RNA Splicing Factors
  • RNA Splicing*
  • RNA, Small Nuclear*
  • Ribonucleoprotein, U4-U6 Small Nuclear / genetics*
  • Ribonucleoprotein, U5 Small Nuclear / genetics
  • Saccharomyces cerevisiae Proteins*
  • Spliceosomes*


  • Fungal Proteins
  • PRP38 protein, S cerevisiae
  • RNA Splicing Factors
  • RNA, Small Nuclear
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • Ribonucleoprotein, U5 Small Nuclear
  • Saccharomyces cerevisiae Proteins