Characterization of the catalytic activity of U2 and U6 snRNAs

RNA. 2003 Jul;9(7):892-904. doi: 10.1261/rna.5440303.

Abstract

Removal of introns from pre-messenger RNAs in eukaryotes is carried out by the spliceosome, an assembly of a large number of proteins and five small nuclear RNAs (snRNAs). We showed previously that an in vitro transcribed and assembled base-paired complex of U2 and U6 snRNA segments catalyzes a reaction that resembles the first step of splicing. Upon incubation with a short RNA oligonucleotide containing the consensus sequence of the pre-mRNA branch site, the U2/U6 complex catalyzed a reaction between the 2' OH of a bulged adenosine and a phosphate in the catalytically important AGC triad of U6, leading to the formation of an X-shaped product, RNA X, apparently linked by an unusual phosphotriester bond. Here we characterize this splicing-related reaction further, showing that RNA X formation is an equilibrium reaction, and that the low yield of the reaction likely reflects an unfavorable equilibrium coefficient. Consistent with a phosphotriester linkage, RNA X is highly alkali-sensitive, but only mildly acid-sensitive. We also show that mutations in the AGC sequence of U6 can have significant effects on RNA X formation, further extending the similarities between splicing and RNA X formation. We also demonstrate that pseudouridylation of U2 enhances RNA X formation, and that U6 snRNA purified from nuclear extracts is capable of forming RNA X. Our data suggest that the ability to form RNA X might be an intrinsic property of spliceosomal snRNAs.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites
  • Catalysis
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism*
  • Transcription, Genetic

Substances

  • RNA, Small Nuclear
  • U2 small nuclear RNA
  • U6 small nuclear RNA