title: REXO2 is an oligoribonuclease active in human mitochondria.
abstract: 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.
authors.affiliation: The Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, The Medical School, Newcastle upon Tyne, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bruni
authors.forename: Pasqua
authors.initials: P
authors.lastname: Gramegna
authors.forename: Jorge M A
authors.initials: JM
authors.lastname: Oliveira
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
authors.forename: Zofia M A
authors.initials: ZM
authors.lastname: Chrzanowska-Lightowlers
mesh_terms: D048948:14-3-3 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005095:Exoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000201:enzymology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009696:Nucleic Acids / Q000737:chemistry; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D024101:Mitochondrial Proteins; D009696:Nucleic Acids; D034741:RNA, Small Interfering; D005095:Exoribonucleases; C413442:SFN protein, human