PDE12 removes mitochondrial RNA poly(A) tails and controls translation in human mitochondria.

TitlePDE12 removes mitochondrial RNA poly(A) tails and controls translation in human mitochondria.
Publication TypeJournal Article
Year of Publication2011
AuthorsRorbach, J, Nicholls, TJJ, Minczuk, MA
JournalNucleic Acids Res
Volume39
Issue17
Pagination7750-63
Date Published2011 Sep 1
ISSN1362-4962
Keywords3' Untranslated Regions, Cell Line, Tumor, Exoribonucleases, Gene Expression Regulation, HEK293 Cells, Humans, Mitochondria, Mitochondrial Proteins, Oxidative Phosphorylation, Poly A, Protein Biosynthesis, Regulatory Sequences, Ribonucleic Acid, Ribonucleases, Ribosomes, RNA, Transgenes
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.

DOI10.1093/nar/gkr470
Alternate JournalNucleic Acids Res.
Citation Key10.1093/nar/gkr470
PubMed ID21666256
PubMed Central IDPMC3177208
Grant ListMC_U105697135 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom