Abstract
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 language | English (US) |
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Pages (from-to) | 1266-1271 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 103 |
Issue number | 5 |
DOIs | |
State | Published - Jan 31 2006 |
Keywords
- RNA splicing
- RNA-binding proteins
- Spliceosome
ASJC Scopus subject areas
- General