REXO2 Is an Oligoribonuclease Active in Human Mitochondria

被引:48
作者
Bruni, Francesco [1 ]
Gramegna, Pasqua [1 ]
Oliveira, Jorge M. A. [3 ]
Lightowlers, Robert N. [2 ]
Chrzanowska-Lightowlers, Zofia M. A. [1 ]
机构
[1] Newcastle Univ, Sch Med, Wellcome Trust Ctr Mitochondrial Res, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[2] Newcastle Univ, Sch Med, Wellcome Trust Ctr Mitochondrial Res, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[3] Univ Porto, Fac Pharm, Dept Drug Sci, REQUIMTE, P-4100 Oporto, Portugal
来源
PLOS ONE | 2013年 / 8卷 / 05期
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
POLYNUCLEOTIDE PHOSPHORYLASE; ESCHERICHIA-COLI; STRANDED-RNA; HUMAN-CELLS; AUG CODONS; DNA; DEGRADATION; NUCLEOIDS; COMPLEX; GENE;
D O I
10.1371/journal.pone.0064670
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Escherichia coli oligoribonuclease, ORN, has a 3' to 5' exonuclease activity specific for small oligomers that is essential for cell viability. The human homologue, REXO2, has hitherto been incompletely characterized, with only its in vitro ability to degrade small single-stranded RNA and DNA fragments documented. Here we show that the human enzyme has clear dual cellular localization being present both in cytosolic and mitochondrial fractions. Interestingly, the mitochondrial form localizes to both the intermembrane space and the matrix. Depletion of REXO2 by RNA interference causes a strong morphological phenotype in human cells, which show a disorganized network of punctate and granular mitochondria. Lack of REXO2 protein also causes a substantial decrease of mitochondrial nucleic acid content and impaired de novo mitochondrial protein synthesis. Our data constitute the first in vivo evidence for an oligoribonuclease activity in human mitochondria.
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页数:11
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