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

被引：43

作者：

Ren, XJ ^{[1
]}

Gavory, G ^{[1
]}

Li, HT ^{[1
]}

Ying, LM ^{[1
]}

Klenerman, D ^{[1
]}

Balasubramanian, S ^{[1
]}

机构：

[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

来源：

NUCLEIC ACIDS RESEARCH | 2003年 / 31卷 / 22期

基金：

英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1093/nar/gkg871

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：6509 / 6515

页数：7

共 37 条

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