A novel RNA pentaloop fold involved in targeting ADAR2.
Adenosine deaminases that act on RNA (ADARs) catalyze the site-specific conversion of adenosine to inosine in primary mRNA transcripts, thereby affecting coding potential of mature mRNAs. Structural determinants that define the adenosine moieties for specific ADARs-mediated deaminations are currently unknown. We report the solution structure of the central region of the human R/G stem-loop pre-mRNA, a natural ADAR2 substrate encoding the subunit B of the glutamate receptor (R/G site). The structure reveals that the GCU(A/C)A pentaloop that is conserved in mammals and birds adopts a novel fold. The fold is stabilized by a complex interplay of hydrogen bonds and stacking interactions. We propose that this new pentaloop structure is an important determinant of the R/G site recognition by ADAR2.
Stefl
Richard
R
Institute of Molecular Biology and Biophysics, Swiss Federal Institute of Technology Zurich, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
Allain
Frédéric H-T
FH
D000243:Adenosine Deaminase / Q000378:metabolism*; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D021122:Protein Subunits / Q000235:genetics; D012322:RNA Precursors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D017470:Receptors, Glutamate / Q000737:chemistry / Q000235:genetics; D013379:Substrate Specificity
D021122:Protein Subunits; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D017470:Receptors, Glutamate; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase