An Upstream Open Reading Frame and the Context of the Two AUG Codons Affect the Abundance of Mitochondrial and Nuclear RNase H1

被引：76

作者：

Suzuki, Yutaka ^{[1
]}

Holmes, J. Bradley ^{[1
,2
]}

Cerritelli, Susana M. ^{[1
]}

Sakhuja, Kiran ^{[1
]}

Minczuk, Michal ^{[2
]}

Holt, Ian J. ^{[2
]}

Crouch, Robert J. ^{[1
]}

机构：

[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA

[2] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2010年 / 30卷 / 21期

基金：

美国国家卫生研究院; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

D O I：

10.1128/MCB.00619-10

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：

RNase H1 in mammalian cells is present in nuclei and mitochondria. Its absence in mitochondria results in embryonic lethality due to the failure to amplify mitochondrial DNA (mtDNA). Dual localization to mitochondria and nuclei results from differential translation initiation at two in-frame AUGs (M1 and M27) of a single mRNA. Here we show that expression levels of the two isoforms depend on the efficiency of translation initiation at each AUG codon and on the presence of a short upstream open reading frame (uORF) resulting in the mitochondrial isoform being about 10% as abundant as the nuclear form. Translation initiation at the M1 AUG is restricted by the uORF, while expression of the nuclear isoform requires reinitiation of ribosomes at the M27 AUG after termination of uORF translation or new initiation by ribosomes skipping the uORF and the M1 AUG. Such translational organization of RNase H1 allows tight control of expression of RNase H1 in mitochondria, where its excess or absence can lead to cell death, without affecting the expression of the nuclear RNase H1.

引用

页码：5123 / 5134

页数：12

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