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首页> 外文期刊>Cell cycle >Telomerase RNA mutated in autosomal dyskeratosis congenita reconstitutes a weakly active telomerase enzyme defective in telomere elongation.
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Telomerase RNA mutated in autosomal dyskeratosis congenita reconstitutes a weakly active telomerase enzyme defective in telomere elongation.

机译：在常染色体异常性角化病先天突变的端粒酶RNA重建了端粒伸长缺陷的弱活性端粒酶。

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Dyskeratosis congenita (DC) is a rare multi-system syndrome characterized by nail dystrophy, abnormal skin pigmentation and mucosal leukoplakia. The gene mutated in the X-linked form of human DC encodes for dyskerin, a nucleolar pseudourydilase that is involved in rRNA maturation. Dyskerin is also involved in telomerase function through its interaction with the telomerase RNA (hTR). Mutations in dyskerin result in low levels of hTR, decreased telomerase activity and telomere shortening. Autosomal dominant DC is characterized by mutations in hTR, supporting the hypothesis that the DC phenotype may be caused by impaired telomere maintenance. Several mutations have been identified in different regions of hTR in patients affected by autosomal dominant DC. Recent reports have shown that coexpression of wild-type hTR with hTR harboring mutations found in the pseudoknot domain does not affect telomerase activity in vitro. However, these studies did not assess the consequences of mutant hTR expression at the telomeres. Here we provide the first direct in vivo evidence that a mutant hTR carrying the GC to AG double substitution in the pseudoknot at nucleotides 107-108 found in patients affected by autosomal dominant DC does not behave as a dominant-negative for telomere maintenance. Rather it reconstitutes a weakly active telomerase enzyme, which is defective in telomere elongation.
机译：先天性角化病（DC）是一种罕见的多系统综合征，其特征是指甲营养不良，皮肤色素沉着异常和粘膜白斑。以人类DC的X连锁形式突变的基因编码dyskerin，dyskerin是参与rRNA成熟的核仁类假尿酸化酶。 Dyskerin还通过与端粒酶RNA（hTR）相互作用来参与端粒酶功能。 dyskerin中的突变导致hTR水平降低，端粒酶活性降低和端粒缩短。常染色体显性DC的特征是hTR突变，支持以下假设：DC表型可能是端粒维持能力受损所致。在常染色体显性DC影响的患者中，已在hTR的不同区域发现了一些突变。最近的报道表明，野生型hTR与在假结域中发现的具有hTR窝藏突变的共表达不会影响体外的端粒酶活性。但是，这些研究并未评估突变型hTR在端粒表达的后果。在这里，我们提供了第一个直接的体内证据，即在常染色体显性DC影响的患者中发现的突变体hTR在假结的107-108位假结中带有GC到AG的双取代，不能作为端粒维持的显性阴性。而是它重建了弱活性的端粒酶，该酶在端粒伸长方面是有缺陷的。

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