Crystal structure of a core spliceosomal protein interface

Matthew J. Schellenberg, Ross A. Edwards, Dustin B. Ritchie, Oliver A. Kent, Monika M. Golas, Holger Stark, Reinhard Lührmann, J. N.Mark Glover, Andrew M. MacMillan

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


The precise excision of introns from precursor mRNAs (pre-mRMAs) in eukaryotes is accomplished by the spliceosome, a complex assembly containing five small nuclear ribonucleoprotein (snRNP) particles. Human p14, a component of the spliceosomal U2 and U11/U12 snRNPs, has been shown to associate directly with the pre-mRNA branch adenosine early in spliceosome assembly and within the fully assembled spliceosome. Here we report the 2.5-Å crystal structure of a complex containing p14 and a peptide derived from the p14-associated U2 snRNP component SF3b155. p14 contains an RNA recognition motif (RRM), the surface of which is largely occluded by a C-terminal α-helix and a portion of the SF3b155 peptide. An analysis of RNA-protein crosslinking to wild-type and mutant p14 shows that the branch adenosine directly interacts with a conserved aromatic within a pocket on the surface of the complex. This result, combined with a comparison of the structure with known RRMs and pseudoRRMs as well as model-building by using the electron cryomicroscopy structure of a spliceosomal U11/U12 di-snRNP, suggests that p14-SF3b155 presents a noncanonical surface for RNA recognition at the heart of the mammalian spliceosome.

Original languageEnglish (US)
Pages (from-to)1266-1271
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - Jan 31 2006


  • RNA splicing
  • RNA-binding proteins
  • Spliceosome

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Crystal structure of a core spliceosomal protein interface'. Together they form a unique fingerprint.

Cite this