Abstract
We have determined the crystal structure of a spliceosomal RNP complex comprising the 15.5kD protein of the human U4/U6.U5 tri-snRNP and the 5' stem-loop of U4 snRNA. The protein interacts almost exclusively with a purine-rich (5+2) internal loop within the 5' stem-loop, giving an unusual RNA fold characterized by two tandem sheared G-A base pairs, a high degree of purine stacking, and the accommodation of a single RNA base, rotated out of the RNA chain, in a pocket of the protein. Apart from yielding the structure of an important entity in the pre-mRNA splicing apparatus, this work also implies a model for the complex of the 15.5kD protein with box C/D snoRNAs. It additionally suggests a general recognition principle in a novel family of RNA binding proteins.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Amino Acid Sequence
- Base Pairing
- Base Sequence
- Crystallography, X-Ray
- Humans
- Models, Molecular
- Molecular Sequence Data
- Molecular Weight
- Nucleic Acid Conformation
- Protein Conformation
- Purines / metabolism
- RNA Precursors / chemistry
- RNA Precursors / genetics
- RNA Precursors / metabolism
- RNA, Small Nuclear / chemistry
- RNA, Small Nuclear / genetics
- RNA, Small Nuclear / metabolism*
- RNA-Binding Proteins / chemistry
- RNA-Binding Proteins / metabolism
- Ribonucleoproteins, Small Nuclear / chemistry*
- Ribonucleoproteins, Small Nuclear / metabolism*
- Ribonucleoproteins, Small Nucleolar / chemistry
- Sequence Alignment
- Spliceosomes / chemistry*
- Spliceosomes / genetics
Substances
- Purines
- RNA Precursors
- RNA, Small Nuclear
- RNA-Binding Proteins
- Ribonucleoproteins, Small Nuclear
- Ribonucleoproteins, Small Nucleolar
- U4 small nuclear RNA