Structural basis for telomerase RNA recognition and RNP assembly by the holoenzyme La family protein p65.
Publication Type:Journal Article
Source:Mol Cell, Volume 47, Issue 1, p.16-26 (2012)
Keywords:Amino Acid Sequence, Base Sequence, Binding Sites, Crystallography, X-Ray, Electrophoretic Mobility Shift Assay, Holoenzymes, Models, Molecular, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Protozoan Proteins, Ribonucleoproteins, RNA, RNA, Protozoan, Sequence Homology, Amino Acid, Telomerase, Tetrahymena thermophila
<p>Telomerase is a ribonucleoprotein complex essential for maintenance of telomere DNA at linear chromosome ends. The catalytic core of Tetrahymena telomerase comprises a ternary complex of telomerase RNA (TER), telomerase reverse transcriptase (TERT), and the essential La family protein p65. NMR and crystal structures of p65 C-terminal domain and its complex with stem IV of TER reveal that RNA recognition is achieved by a combination of single- and double-stranded RNA binding, which induces a 105° bend in TER. The domain is a cryptic, atypical RNA recognition motif with a disordered C-terminal extension that forms an α helix in the complex necessary for hierarchical assembly of TERT with p65-TER. This work provides the first structural insight into biogenesis and assembly of TER with a telomerase-specific protein. Additionally, our studies define a structurally homologous domain (xRRM) in genuine La and LARP7 proteins and suggest a general mode of RNA binding for biogenesis of their diverse RNA targets.</p>