title: PDE12 removes mitochondrial RNA poly(A) tails and controls translation in human mitochondria.
abstract: Polyadenylation of mRNA in human mitochondria is crucial for gene expression and perturbation of poly(A) tail length has been linked to a human neurodegenerative disease. Here we show that 2'-phosphodiesterase (2'-PDE), (hereafter PDE12), is a mitochondrial protein that specifically removes poly(A) extensions from mitochondrial mRNAs both in vitro and in mitochondria of cultured cells. In eukaryotes, poly(A) tails generally stabilize mature mRNAs, whereas in bacteria they increase mRNA turnover. In human mitochondria, the effects of increased PDE12 expression were transcript dependent. An excess of PDE12 led to an increase in the level of three mt-mRNAs (ND1, ND2 and CytB) and two (CO1 and CO2) were less abundant than in mitochondria of control cells and there was no appreciable effect on the steady-state level of the remainder of the mitochondrial transcripts. The alterations in poly(A) tail length accompanying elevated PDE12 expression were associated with severe inhibition of mitochondrial protein synthesis, and consequently respiratory incompetence. Therefore, we propose that mRNA poly(A) tails are important in regulating protein synthesis in human mitochondria, as it is the case for nuclear-encoded eukaryotic mRNA.
authors.affiliation: MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rorbach
authors.forename: Thomas J J
authors.initials: TJ
authors.lastname: Nicholls
authors.forename: Michal
authors.initials: M
authors.lastname: Minczuk
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D005095:Exoribonucleases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D011061:Poly A / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism*; D000077278:RNA, Mitochondrial; D038621:Regulatory Sequences, Ribonucleic Acid; D012260:Ribonucleases / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D019076:Transgenes
chemical_list: D020413:3' Untranslated Regions; D024101:Mitochondrial Proteins; D000077278:RNA, Mitochondrial; D038621:Regulatory Sequences, Ribonucleic Acid; D011061:Poly A; D012313:RNA; D005095:Exoribonucleases; D012260:Ribonucleases; C445084:mRNA deadenylase; C568404:PDE12 protein, human