Nucleic Acids Research, 2003, Vol. 31, No. 10 2614-2621
© 2003 Oxford University Press
The solution structure of an essential stem–loop of human telomerase RNA
Department of Biochemistry and Department of Chemistry, University of Washington, Seattle WA 98195-1700, USA and 1 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
Nicolas Leulliot, LURE, bat 209 Universite’ Paris Sud, Orsay 91898, France
The ribonucleoprotein enzyme telomerase maintains chromosome ends in most eukaryotes and is critical for a cell’s genetic stability and its proliferative viability. All telomerases contain a catalytic protein component homologous to viral reverse transcriptases (TERT) and an RNA (TR) that provides the template sequence as well as a scaffold for ribonucleoprotein assembly. Vertebrate telomerase RNAs have three essential domains: the template, activation and stability domains. Here we report the NMR structure of an essential RNA element derived from the human telomerase RNA activation domain. The sequence forms a stem–loop structure stabilized by a GU wobble pair formed by two of the five unpaired residues capping a short double helical region. The remaining three loop residues are in a well-defined conformation and form phosphate-base stacking interactions reminiscent of other RNA loop structures. Mutations of these unpaired nucleotides abolish enzymatic activity. The structure rationalizes a number of biochemical observations, and allows us to propose how the loop may function in the telomerase catalytic cycle. The pre-formed structure of the loop exposes the bases of these three essential nucleotides and positions them to interact with other RNA sequences within TR, with the reverse transcriptase or with the newly synthesized telomeric DNA strand. The functional role of this stem–loop appears to be conserved in even distantly related organisms such as yeast and ciliates.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Miller, L. E. Jones, K. Giovannitti, D. Piper, and M. J. Serra Thermodynamic analysis of 5' and 3' single- and 3' double-nucleotide overhangs neighboring wobble terminal base pairs Nucleic Acids Res., October 1, 2008; 36(17): 5652 - 5659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Podlevsky, C. J. Bley, R. V. Omana, X. Qi, and J. J.-L. Chen The Telomerase Database Nucleic Acids Res., January 11, 2008; 36(suppl_1): D339 - D343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Brown, M. Abraham, S. Pearl, M. M. Kabaha, E. Elboher, and Y. Tzfati A critical three-way junction is conserved in budding yeast and vertebrate telomerase RNAs Nucleic Acids Res., September 25, 2007; 35(18): 6280 - 6289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, H. Nishizuka, K. Tsutsumi, Y. Imai, Y. Kurihara, and S. Uesugi Structure, Interactions and Effects on Activity of the 5'-terminal Region of Human telomerase RNA J. Biochem., May 1, 2007; 141(5): 755 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. LEEPER and G. VARANI The structure of an enzyme-activating fragment of human telomerase RNA RNA, April 1, 2005; 11(4): 394 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ly, R. T. Calado, P. Allard, G. M. Baerlocher, P. M. Lansdorp, N. S. Young, and T. G. Parslow Functional characterization of telomerase RNA variants found in patients with hematologic disorders Blood, March 15, 2005; 105(6): 2332 - 2339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. UEDA and R. W. ROBERTS Analysis of a long-range interaction between conserved domains of human telomerase RNA RNA, January 1, 2004; 10(1): 139 - 147. [Abstract] [Full Text] [PDF]
|
|