Abstract
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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Base Sequence
-
Binding Sites / genetics
-
Crystallography, X-Ray
-
Electrophoretic Mobility Shift Assay
-
Holoenzymes / chemistry
-
Holoenzymes / genetics
-
Holoenzymes / metabolism
-
Models, Molecular
-
Molecular Sequence Data
-
Mutation
-
Nucleic Acid Conformation
-
Protein Binding
-
Protein Structure, Secondary
-
Protein Structure, Tertiary
-
Protozoan Proteins / chemistry*
-
Protozoan Proteins / genetics
-
Protozoan Proteins / metabolism
-
RNA / chemistry*
-
RNA / genetics
-
RNA / metabolism
-
RNA, Protozoan / chemistry*
-
RNA, Protozoan / genetics
-
RNA, Protozoan / metabolism
-
Ribonucleoproteins / chemistry*
-
Ribonucleoproteins / genetics
-
Ribonucleoproteins / metabolism
-
Sequence Homology, Amino Acid
-
Telomerase / chemistry*
-
Telomerase / genetics
-
Telomerase / metabolism
-
Tetrahymena thermophila / enzymology
-
Tetrahymena thermophila / genetics
Substances
-
Holoenzymes
-
Protozoan Proteins
-
RNA, Protozoan
-
Ribonucleoproteins
-
telomerase RNA
-
RNA
-
Telomerase
Associated data
-
PDB/2LSL
-
PDB/4ERD
-
PDB/4EYT