Triple-helix structure in telomerase RNA contributes to catalysis.
Telomerase is responsible for replication of the ends of linear chromosomes in most eukaryotes. Its intrinsic RNA subunit provides the template for synthesis of telomeric DNA by the reverse-transcriptase (TERT) subunit and tethers other proteins into the ribonucleoprotein (RNP) complex. We report that a phylogenetically conserved triple helix within a pseudoknot structure of this RNA contributes to telomerase activity but not by binding the TERT protein. Instead, 2'-OH groups protruding from the triple helix participate in both yeast and human telomerase catalysis; they may orient the primer-template relative to the active site in a manner analogous to group I ribozymes. The role of RNA in telomerase catalysis may have been acquired relatively recently or, alternatively, telomerase may be a molecular fossil representing an evolutionary link between RNA enzymes and RNP enzymes.
Qiao
Feng
F
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, Campus Box 215, University of Colorado, Boulder, Colorado 80309-0215, USA.
Cech
Thomas R
TR
D001665:Binding Sites; D002384:Catalysis; D006801:Humans; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D019098:Telomerase / Q000737:chemistry* / Q000378:metabolism; D015003:Yeasts
C422952:telomerase RNA; D012313:RNA; D019098:Telomerase