Sculpting of the spliceosomal branch site recognition motif by a conserved pseudouridine.
Pairing of a consensus sequence of the precursor (pre)-mRNA intron with a short region of the U2 small nuclear (sn)RNA during assembly of the eukaryotic spliceosome results in formation of a complementary helix of seven base pairs with a single unpaired adenosine residue. The 2' OH of this adenosine, called the branch site, brings about nucleophilic attack at the pre-mRNA 5' splice site in the first step of splicing. Another feature of this pairing is the phylogenetic conservation of a pseudouridine (psi) residue in U2 snRNA nearly opposite the branch site. We show that the presence of this psi in the pre-mRNA branch-site helix of Saccharomyces cerevisiae induces a dramatically altered architectural landscape compared with that of its unmodified counterpart. The psi-induced structure places the nucleophile in an accessible position for the first step of splicing.
Newby
Meredith I
MI
Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306-4390, USA.
Greenbaum
Nancy L
NL
D000241:Adenosine / Q000737:chemistry; D001483:Base Sequence; D001665:Binding Sites; D007438:Introns; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D011560:Pseudouridine / Q000737:chemistry* / Q000235:genetics; D012322:RNA Precursors / Q000737:chemistry; D012326:RNA Splicing; D012331:RNA, Fungal / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017381:Spliceosomes / Q000737:chemistry*; D014529:Uridine / Q000737:chemistry
D012322:RNA Precursors; D012331:RNA, Fungal; D011560:Pseudouridine; D000241:Adenosine; D014529:Uridine