HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Identification of a new RNA.RNA interaction site for human telomerase RNA (hTR): structural implications for hTR accumulation and a dyskeratosis congenita point mutation.

Abstract
The enzyme telomerase is a ribonucleoprotein that has a critical role in the maintenance of stable telomeres in organisms that possess linear chromosomes. Using a recently developed single molecule fluorescence coincidence method, we have studied the RNA component of telomerase (hTR) and directly observed multimerisation of hTR in solution. RNA mutagenesis and blocking oligonucleotides were employed to identify the single-stranded internal loop J7b/8a as an important and specific hTR.hTR interaction site. This observation was confirmed by studies on a model RNA fragment (hTR(380-444)), comprising part of the H/ACA domain, the internal loop J7b/8a and the CR7 domain, that was found to dimerise. Substitution mutagenesis within the proposed RNA.RNA interaction site of hTR(380-444) resulted in a loss of dimerisation potential and insertion of the dyskeratosis congenita mutation C408G led to a significant reduction in dimer formation. Together, these results suggest that this RNA.RNA interaction site may be functionally relevant.
AuthorsXiaojun Ren, Gérald Gavory, Haitao Li, Liming Ying, David Klenerman, Shankar Balasubramanian
JournalNucleic acids research (Nucleic Acids Res) Vol. 31 Issue 22 Pg. 6509-15 (Nov 15 2003) ISSN: 1362-4962 [Electronic] England
PMID14602909 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA
  • Telomerase
Topics
  • Binding Sites (genetics)
  • Dimerization
  • Dyskeratosis Congenita (enzymology, genetics)
  • Electrophoresis, Agar Gel
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Point Mutation
  • RNA (chemistry, genetics, metabolism)
  • Spectrometry, Fluorescence (methods)
  • Telomerase (chemistry, genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: