Targeting of the cytosolic poly(A) binding protein PABPC1 to mitochondria causes mitochondrial translation inhibition.
Mammalian mitochondria contain their own genome that is almost fully transcribed from both strands, generating polycistronic RNA units that are processed and matured. The mitochondrial mRNA is modified by oligo- or polyadenylation at the 3' termini, but the exact function of this post-transcriptional addition is unclear. Current debate focuses on the role of polyadenylation in transcript stability. An equally likely function that has received little attention is that, as in the cytosol of eukaryotes, polyadenylation facilitates translation in the mitochondrion. To address this issue, we have targeted cytosolic proteins to the mitochondrion, a poly(A) specific 3' exoribonuclease, mtPARN, and a poly(A)binding protein, mtPABP1. Removal of the 3' adenylyl extensions had a variable effect on mt-mRNA steady-state levels, increasing (MTND1, 2, 5) or decreasing (MTCO1, 2, RNA14) certain species with minimal effect on others (RNA7, MTND3). Translation was markedly affected, but interpretation of this was complicated by the concomitant 3' truncation of the open reading frame in most cases. Coating of the poly(A) tail by mtPABP1, however, did not lead to transcript decay but caused a marked inhibition of mitochondrial translation. These data are consistent with endogenous RNA-binding factor(s) interacting with the poly(A) to optimize mitochondrial protein synthesis.
Wydro
Mateusz
M
Mitochondrial Research Group, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Bobrowicz
Agnieszka
A
Temperley
Richard J
RJ
Lightowlers
Robert N
RN
Chrzanowska-Lightowlers
Zofia M
ZM
D002460:Cell Line; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D011061:Poly A / Q000378:metabolism; D039122:Poly(A)-Binding Protein I / Q000378:metabolism*; D014176:Protein Biosynthesis; D021381:Protein Transport; D012313:RNA / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D000077278:RNA, Mitochondrial
D045222:Electron Transport Chain Complex Proteins; D005095:Exoribonucleases; D024101:Mitochondrial Proteins; D011061:Poly A; D039122:Poly(A)-Binding Protein I; D012313:RNA; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial