Nucleic Acids Research, 2002, Vol. 30, No. 4 912-920
© 2002 Oxford University Press
Analysis of the structure of human telomerase RNA in vivo
1Biological Research Center, Hungarian Academy of Sciences, PO Box 521, H-6701 Szeged, Hungary and 2Laboratoire de Biologie Moléculaire Eucaryote du CNRS, 118 route de Narbonne, 31062 Toulouse, France
Telomerase is a ribonucleoprotein reverse transcriptase that synthesises telomeric DNA. The RNA component of telomerase acts as a template for telomere synthesis and binds the reverse transcriptase. In this study, we have performed in vivo and in vitro structural analyses of human telomerase RNA (hTR). In vivo mapping experiments showed that the 5'-terminal template domain of hTR folds into a long hairpin structure, in which the template sequence occupies a readily accessible position. Intriguingly, neither in vivo nor in vitro mapping of hTR confirmed formation of a stable ‘pseudoknot’ helix, suggesting that this functionally essential long range interaction is formed only temporarily. In vitro control mappings demonstrated that the 5'-terminal template domain of hTR cannot fold correctly in the absence of cellular protein factors. The 3'-terminal domain of hTR, both in vivo and in vitro, folds into the previously predicted box H/ACA snoRNA-like ‘hairpin–hinge–hairpin–tail’ structure. Finally, comparison of the in vivo and in vitro modification patterns of hTR revealed several regions that might be directly involved in binding of telomerase reverse transcriptase or other telomerase proteins.
* To whom correspondence should be addressed at: Laboratoire de Biologie Moléculaire Eucaryote du CNRS, 118 route de Narbonne, 31062 Toulouse, France. Tel: +33 5 61 33 59 91; Fax: +33 5 61 33 58 86; Email: tamas{at}ibcg.biotoul.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Chen, J.-D. Wen, and I. Tinoco Jr Single-molecule mechanical unfolding and folding of a pseudoknot in human telomerase RNA RNA, December 1, 2007; 13(12): 2175 - 2188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. B. Ulyanov, K. Shefer, T. L. James, and Y. Tzfati Pseudoknot structures with conserved base triples in telomerase RNAs of ciliates Nucleic Acids Res., September 25, 2007; 35(18): 6150 - 6160. [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. KISS, E. FAYET, B.E. JADY, P. RICHARD, and M. WEBER Biogenesis and Intranuclear Trafficking of Human Box C/D and H/ACA RNPs Cold Spring Harb Symp Quant Biol, January 1, 2006; 71(0): 407 - 417. [Abstract] [PDF]
|
|
|
|
|
|
S. Cao and S.-J. Chen Predicting RNA pseudoknot folding thermodynamics. Nucleic Acids Res., January 1, 2006; 34(9): 2634 - 2652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Marie-Egyptienne, M. A. Cerone, J. A. Londono-Vallejo, and C. Autexier A human-Tetrahymena pseudoknot chimeric telomerase RNA reconstitutes a nonprocessive enzyme in vitro that is defective in telomere elongation Nucleic Acids Res., September 28, 2005; 33(17): 5446 - 5457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. MORIARTY, D. T. MARIE-EGYPTIENNE, and C. AUTEXIER Regulation of 5' template usage and incorporation of noncognate nucleotides by human telomerase RNA, September 1, 2005; 11(9): 1448 - 1460. [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]
|
|
|
|
|
|
K. Moran-Jones, L. Wayman, D. D. Kennedy, R. R. Reddel, S. Sara, M. J. Snee, and R. Smith hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere Nucleic Acids Res., January 19, 2005; 33(2): 486 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sobczak and W. J. Krzyzosiak Imperfect CAG Repeats Form Diverse Structures in SCA1 Transcripts J. Biol. Chem., October 1, 2004; 279(40): 41563 - 41572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Chappell and V. Lundblad Structural Elements Required for Association of the Saccharomyces cerevisiae Telomerase RNA with the Est2 Reverse Transcriptase Mol. Cell. Biol., September 1, 2004; 24(17): 7720 - 7736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Park, R. Vepachedu, R. A. Owens, and J. M. Vivanco The N-Glycosidase Activity of the Ribosome-inactivating Protein ME1 Targets Single-stranded Regions of Nucleic Acids Independent of Sequence or Structural Motifs J. Biol. Chem., August 13, 2004; 279(33): 34165 - 34174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Moriarty, D. T. Marie-Egyptienne, and C. Autexier Functional Organization of Repeat Addition Processivity and DNA Synthesis Determinants in the Human Telomerase Multimer Mol. Cell. Biol., May 1, 2004; 24(9): 3720 - 3733. [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]
|
|
|
|
|
|
C. A. THEIMER, L. D. FINGER, and J. FEIGON YNMG tetraloop formation by a dyskeratosis congenita mutation in human telomerase RNA RNA, December 1, 2003; 9(12): 1446 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ly, E. H. Blackburn, and T. G. Parslow Comprehensive Structure-Function Analysis of the Core Domain of Human Telomerase RNA Mol. Cell. Biol., October 1, 2003; 23(19): 6849 - 6856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tzfati, Z. Knight, J. Roy, and E. H. Blackburn A novel pseudoknot element is essential for the action of a yeast telomerase Genes & Dev., July 15, 2003; 17(14): 1779 - 1788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Leeper, N. Leulliot, and G. Varani The solution structure of an essential stem-loop of human telomerase RNA Nucleic Acids Res., May 15, 2003; 31(10): 2614 - 2621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ly, L. Xu, M. A. Rivera, T. G. Parslow, and E. H. Blackburn A role for a novel `trans-pseudoknot' RNA-RNA interaction in the functional dimerization of human telomerase Genes & Dev., May 1, 2003; 17(9): 1078 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Theimer, L. D. Finger, L. Trantirek, and J. Feigon Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA PNAS, January 21, 2003; 100(2): 449 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Comolli, I. Smirnov, L. Xu, E. H. Blackburn, and T. L. James A molecular switch underlies a human telomerase disease PNAS, December 24, 2002; 99(26): 16998 - 17003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gavory, M. Farrow, and S. Balasubramanian Minimum length requirement of the alignment domain of human telomerase RNA to sustain catalytic activity in vitro Nucleic Acids Res., October 15, 2002; 30(20): 4470 - 4480. [Abstract] [Full Text] [PDF]
|
|