Summary information and primary citation
- PDB-id
- 4pkd; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- gene regulation
- Method
- X-ray (2.5 Å)
- Summary
- U1-70k in complex with u1 snrna stem-loops 1 and u1-a rrm in complex with stem-loop 2
- Reference
- Kondo Y, Oubridge C, van Roon AM, Nagai K (2015): "Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition." Elife, 4. doi: 10.7554/eLife.04986.
- Abstract
- U1 snRNP binds to the 5' exon-intron junction of pre-mRNA and thus plays a crucial role at an early stage of pre-mRNA splicing. We present two crystal structures of engineered U1 sub-structures, which together reveal at atomic resolution an almost complete network of protein-protein and RNA-protein interactions within U1 snRNP, and show how the 5' splice site of pre-mRNA is recognised by U1 snRNP. The zinc-finger of U1-C interacts with the duplex between pre-mRNA and the 5'-end of U1 snRNA. The binding of the RNA duplex is stabilized by hydrogen bonds and electrostatic interactions between U1-C and the RNA backbone around the splice junction but U1-C makes no base-specific contacts with pre-mRNA. The structure, together with RNA binding assays, shows that the selection of 5'-splice site nucleotides by U1 snRNP is achieved predominantly through basepairing with U1 snRNA whilst U1-C fine-tunes relative affinities of mismatched 5'-splice sites.
