Structural basis for telomerase RNA recognition and RNP assembly by the holoenzyme La family protein p65

Mol Cell. 2012 Jul 13;47(1):16-26. doi: 10.1016/j.molcel.2012.05.018. Epub 2012 Jun 14.

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.

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