title: Specificity of ribonucleoprotein interaction determined by RNA folding during complex formulation.
abstract: Many proteins involved in pre-mRNA processing contain one or more copies of a 70-90-amino-acid alphabeta module called the ribonucleoprotein domain. RNA maturation depends on the specific recognition by ribonucleoproteins of RNA elements within pre-mRNAs and small nuclear RNAs. The human U1A protein binds an RNA hairpin during splicing, and regulates its own expression by binding an internal loop in the 3'-untranslated region of its pre-mRNA, preventing polyadenylation. Here we report the nuclear magnetic resonance structure of the complex between the regulatory element of the U1A 3'-untranslated region (UTR) and the U1A protein RNA-binding domain. Specific intermolecular recognition requires the interaction of the variable loops of the ribonucleoprotein domain with the well-structured helical regions of the RNA. Formation of the complex then orders the flexible RNA single-stranded loop against the protein beta-sheet surface, and reorganizes the carboxy-terminal region of the protein to maximize surface complementarity and functional group recognition.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: F H
authors.initials: FH
authors.lastname: Allain
authors.forename: C C
authors.initials: CC
authors.lastname: Gubser
authors.forename: P W
authors.initials: PW
authors.lastname: Howe
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: D
authors.initials: D
authors.lastname: Neuhaus
authors.forename: G
authors.initials: G
authors.lastname: Varani
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C075339:U1A protein; D012313:RNA