Structural basis for protein-RNA recognition in telomerase

Nat Struct Mol Biol. 2014 Jun;21(6):507-12. doi: 10.1038/nsmb.2819. Epub 2014 May 4.

Abstract

Telomerase is a large ribonucleoprotein complex minimally composed of a catalytic telomerase reverse transcriptase (TERT) and an RNA component (TR) that provides the template for telomeric DNA synthesis. However, it remains unclear how TERT and TR assemble into a functional telomerase. Here we report the crystal structure of the conserved regions 4 and 5 (CR4/5) of TR in complex with the TR-binding domain (TRBD) of TERT from the teleost fish Oryzias latipes. The structure shows that CR4/5 adopts an L-shaped three-way-junction conformation with its two arms clamping onto TRBD. Both the sequence and conformation of CR4/5 are required for the interaction. Our structural and mutational analyses suggest that the observed CR4/5-TRBD recognition is common to most eukaryotes, and CR4/5 in vertebrate TR might have a similar role in telomerase regulation as that of stem-loop IV in Tetrahymena TR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Oryzias / genetics*
  • Protein Structure, Tertiary
  • RNA / chemistry*
  • Sequence Homology
  • Telomerase / chemistry*
  • Telomerase / physiology*

Substances

  • RNA
  • Telomerase

Associated data

  • PDB/4O26