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Published on: March 14, 2014
PDE12 removes mitochondrial RNA poly(A) tails and controls translation in human mitochondria
Joanna Rorbach1, Thomas J J Nicholls, Michal Minczuk
1MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK.
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.
Insights
Mitochondrial 2'-phosphodiesterase (PDE12) removes poly(A) tails from mitochondrial mRNAs, impacting gene expression. Altered poly(A) tail length affects protein synthesis and respiratory function, highlighting their regulatory role.
Area of Science:
- Mitochondrial biology
- Molecular genetics
- Biochemistry
Background:
- Polyadenylation of mRNA in human mitochondria is vital for gene expression.
- Dysregulation of poly(A) tail length is implicated in neurodegenerative diseases.
- Mitochondrial gene expression regulation is complex and not fully understood.
Purpose of the Study:
- To identify proteins involved in mitochondrial mRNA poly(A) tail processing.
- To investigate the function of 2 -phosphodiesterase (PDE12) in human mitochondria.
- To elucidate the role of mRNA poly(A) tails in mitochondrial gene expression and function.
Main Methods:
- In vitro enzymatic assays to assess PDE12 activity on polyadenylated RNA.
- Cell culture experiments to study PDE12 expression and its effects on mitochondrial transcripts.
- Analysis of mitochondrial mRNA levels, poly(A) tail lengths, and protein synthesis.
Main Results:
- PDE12 was identified as a mitochondrial protein that specifically removes poly(A) extensions from mitochondrial mRNAs.
- Increased PDE12 expression led to transcript-dependent alterations in mt-mRNA levels.
- Changes in poly(A) tail length correlated with inhibited mitochondrial protein synthesis and respiratory incompetence.
Conclusions:
- mRNA poly(A) tails play a crucial role in regulating protein synthesis in human mitochondria.
- PDE12 is a key enzyme in controlling mitochondrial mRNA poly(A) tail length and, consequently, mitochondrial function.
- This study provides new insights into the post-transcriptional regulation of mitochondrial gene expression.
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