Upstream open reading frames: Molecular switches in (patho)physiology

被引：134

作者：

Wethmar, Klaus ^{[1
,2
]}

Smink, Jeske J. ^{[1
]}

Leutz, Achim ^{[1
]}

机构：

[1] Max Delbrueck Ctr Mol Med, Berlin, Germany

[2] Univ Med Berlin, Berlin, Germany

来源：

BIOESSAYS | 2010年 / 32卷 / 10期

关键词：

C/EBP; mutations; translational control; tumorigenesis; uORF; BINDING PROTEIN-ALPHA; TRANSCRIPTION FACTOR-C/EBP; ACUTE MYELOID-LEUKEMIA; ENRICHED INHIBITORY PROTEIN; MESSENGER-RNA TRANSLATION; AUG INITIATOR CODON; BETA ISOFORM; EUKARYOTIC RIBOSOMES; GENE-EXPRESSION; GRANULOCYTIC DIFFERENTIATION;

D O I：

10.1002/bies.201000037

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：

Conserved upstream open reading frames (uORFs) are found within many eukaryotic transcripts and are known to regulate protein translation. Evidence from genetic and bioinformatic studies implicates disturbed uORF-mediated translational control in the etiology of human diseases. A genetic mouse model has recently provided proof-of-principle support for the physiological relevance of uORF-mediated translational control in mammals. The targeted disruption of the uORF initiation codon within the transcription factor CCAAT/enhancer binding protein beta (C/EBP beta) gene resulted in deregulated C/EBP beta protein isoform expression, associated with defective liver regeneration and impaired osteoclast differentiation. The high prevalence of uORFs in the human transcriptome suggests that intensified search for mutations within 5' RNA leader regions may reveal a multitude of alterations affecting uORFs, causing pathogenic deregulation of protein expression.

引用

页码：885 / 893

页数：9

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