Structural basis of the interaction between P-element somatic inhibitor and U1-70k essential for the alternative splicing of P-element transposase.
P-element transposition in Drosophila is regulated by tissue-specific alternative splicing of the P-element transposase pre-mRNA. In somatic cells, the P-element somatic inhibitor (PSI) protein binds to exon 3 of the pre-mRNA and recruits U1 small nuclear ribonucleoprotein (snRNP) to the F1 pseudo-splice site. This abrogates binding of U1 snRNP to the genuine 5' splice site, thereby preventing excision of the third intron. Two homologous short sequences, referred to as the A and B boxes, near the C terminus of PSI bind to U1-70k protein within U1 snRNP. We have now mapped the AB box-binding site of U1-70k to a short proline-rich sequence at the C terminus. Our NMR study shows that the B box forms an anti-parallel helical hairpin in which four highly conserved aromatic residues form a cluster on one face of the first helix. This hydrophobic cluster interacts extensively with the proline-rich region of the U1-70k protein.
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Tijana
T
Ignjatovic
Ji-Chun
JC
Yang
Jonathan
J
Butler
David
D
Neuhaus
Kiyoshi
K
Nagai
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D005091:Exons; D007438:Introns; D009682:Magnetic Resonance Spectroscopy; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D012322:RNA Precursors; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism*; D019895:Transposases / Q000235:genetics*
D029721:Drosophila Proteins; D009687:Nuclear Proteins; C092281:PSI protein, Drosophila; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D019895:Transposases