4PKD

U1-70k in complex with U1 snRNA stem-loops 1 and U1-A RRM in complex with stem-loop 2

Summary for 4PKD

• Entry DOI: 10.2210/pdb4pkd/pdb
• Related: 1URN 3CW1 3PGW
• Descriptor: U1 snRNA stem-loops 1 and 2 (55-MER), U1 small nuclear ribonucleoprotein A,U1 small nuclear ribonucleoprotein 70 kDa, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: u1-70k, u1 snrnp, pre-mrna splicing, spliceosome, gene regulation
• Biological source: Sus scrofa (Pig); More
• Cellular location: Nucleus: P08621
• Total number of polymer chains: 2
• Total formula weight: 50112.00

Authors

Oubridge, C.,Kondo, Y.,van Roon, A.M.,Nagai, K. (deposition date: 2014-05-14, release date: 2014-12-31, Last modification date: 2023-12-20)

Primary citation

Kondo, Y.,Oubridge, C.,van Roon, A.M.,Nagai, K.
Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition.
Elife, 4:-, 2015

PubMed 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.

PubMed: 25555158
DOI: 10.7554/eLife.04986

Experimental method

X-RAY DIFFRACTION (2.5 Å)