Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition

Elife. 2015 Jan 2:4:e04986. doi: 10.7554/eLife.04986.


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.

Keywords: 5′ splice site; U1 snRNP; biophysics; crystallography; human; pre-mRNA splicing; spliceosome; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Nucleic Acid Conformation
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Binding
  • RNA Splice Sites*
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / metabolism
  • Ribonucleoprotein, U1 Small Nuclear / chemistry*
  • Ribonucleoprotein, U1 Small Nuclear / metabolism*


  • Peptides
  • RNA Splice Sites
  • RNA, Small Nuclear
  • Ribonucleoprotein, U1 Small Nuclear
  • U1 small nuclear RNA