1na2

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{{STRUCTURE_1na2| PDB=1na2 | SCENE= }}
{{STRUCTURE_1na2| PDB=1na2 | SCENE= }}
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'''Solution structure of the p2b hairpin from human telomerase RNA'''
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===Solution structure of the p2b hairpin from human telomerase RNA===
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==Overview==
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Autosomal dominant dyskeratosis congenita (DKC), as well as aplastic anemia, has been linked to mutations in the RNA component of telomerase, the ribonucleoprotein responsible for telomere maintenance. Here we examine the effect of the DKC mutations on the structure and stability of human telomerase RNA pseudoknot and CR7 domains by using NMR and thermal melting. The CR7 domain point mutation decreases stability and alters a conserved secondary structure thought to be involved in human telomerase RNA accumulation in vivo. We find that pseudoknot constructs containing the conserved elements of the pseudoknot domain are in equilibrium with a hairpin conformation. The solution structure of the wild-type hairpin reveals that it forms a continuous helix containing a novel run of three consecutive U.U and a U.C base pairs closed by a pentaloop. The six base pairs unique to the hairpin conformation are phylogenetically conserved in mammals, suggesting that this conformation is also functionally important. The DKC mutation in the pseudoknot domain results in a shift in the equilibrium toward the hairpin form, primarily due to destabilization of the pseudoknot. Our results provide insight into the effect of these mutations on telomerase structure and suggest that the catalytic cycle of telomerase involves a delicate interplay between RNA conformational states, alteration of which leads to the disease state.
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{{ABSTRACT_PUBMED_12525685}}
==About this Structure==
==About this Structure==
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NA2 OCA].
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Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NA2 OCA].
==Reference==
==Reference==
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[[Category: U-c base pair]]
[[Category: U-c base pair]]
[[Category: U-u base pair]]
[[Category: U-u base pair]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:16:52 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:03:23 2008''

Revision as of 01:03, 28 July 2008

Image:1na2.png

Template:STRUCTURE 1na2

Solution structure of the p2b hairpin from human telomerase RNA

Template:ABSTRACT PUBMED 12525685

About this Structure

Full experimental information is available from OCA.

Reference

Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA., Theimer CA, Finger LD, Trantirek L, Feigon J, Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):449-54. Epub 2003 Jan 13. PMID:12525685

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