Zebrafish Models for Dyskeratosis Congenita Reveal Critical Roles of p53   Activation Contributing to Hematopoietic Defects through RNA Processing

doi:10.1371/journal.pone.0030188

CORC > 北京大学 > 生命科学学院

	Zebrafish Models for Dyskeratosis Congenita Reveal Critical Roles of p53 Activation Contributing to Hematopoietic Defects through RNA Processing
	Zhang, Ying ; Morimoto, Kenji ; Danilova, Nadia ; Zhang, Bo ; Lin, Shuo
刊名	plos one
	2012
关键词	TELOMERASE COMPONENT GENE MUTATIONS PROTEIN STRESS CANCER LENGTH RIBONUCLEOPROTEINS EXPRESSION SNORNPS
DOI	10.1371/journal.pone.0030188
英文摘要	Dyskeratosis congenita (DC) is a rare bone marrow failure syndrome in which hematopoietic defects are the main cause of mortality. The most studied gene responsible for DC pathogenesis is DKC1 while mutations in several other genes encoding components of the H/ACA RNP telomerase complex, which is involved in ribosomal RNA(rRNA) processing and telomere maintenance, have also been implicated. GAR1/nola1 is one of the four core proteins of the H/ACA RNP complex. Through comparative analysis of morpholino oligonucleotide induced knockdown of dkc1 and a retrovirus insertion induced mutation of GAR1/nola1 in zebrafish, we demonstrate that hematopoietic defects are specifically recapitulated in these models and that these defects are significantly reduced in a p53 null mutant background. We further show that changes in telomerase activity are undetectable at the early stages of DC pathogenesis but rRNA processing is clearly defective. Our data therefore support a model that deficiency in dkc1 and nola1 in the H/ACA RNP complex likely contributes to the hematopoietic phenotype through p53 activation associated with rRNA processing defects rather than telomerase deficiency during the initial stage of DC pathogenesis.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000301704200009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Multidisciplinary Sciences; SCI(E); PubMed; 13; ARTICLE; 1; e30188; 7
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/343240]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhang, Ying,Morimoto, Kenji,Danilova, Nadia,et al. Zebrafish Models for Dyskeratosis Congenita Reveal Critical Roles of p53 Activation Contributing to Hematopoietic Defects through RNA Processing[J]. plos one,2012.
APA	Zhang, Ying,Morimoto, Kenji,Danilova, Nadia,Zhang, Bo,&Lin, Shuo.(2012).Zebrafish Models for Dyskeratosis Congenita Reveal Critical Roles of p53 Activation Contributing to Hematopoietic Defects through RNA Processing.plos one.
MLA	Zhang, Ying,et al."Zebrafish Models for Dyskeratosis Congenita Reveal Critical Roles of p53 Activation Contributing to Hematopoietic Defects through RNA Processing".plos one (2012).