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Mitochondrial transcript maturation and its disorders.

Van Haute L, Pearce SF, Powell CA, D'Souza AR, Nicholls TJ, Minczuk M - J. Inherit. Metab. Dis. (2015)

Bottom Line: Additionally, mutations in mtDNA-encoded genes may also affect RNA maturation and are frequently associated with human disease.We review the current knowledge on a subset of nuclear-encoded genes coding for proteins involved in mitochondrial RNA maturation, for which genetic variants impacting upon mitochondrial pathophysiology have been reported.Also, primary pathological mtDNA mutations with recognised effects upon RNA processing are described.

View Article: PubMed Central - PubMed

Affiliation: MRC Mitochondrial Biology Unit, Hills Road, Cambridge, CB2 0XY, UK.

ABSTRACT
Mitochondrial respiratory chain deficiencies exhibit a wide spectrum of clinical presentations owing to defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mitochondrial DNA (mtDNA) or mutations in nuclear genes coding for mitochondrially-targeted proteins. The underlying pathomechanisms can affect numerous pathways involved in mitochondrial biology including expression of mtDNA-encoded genes. Expression of the mitochondrial genes is extensively regulated at the post-transcriptional stage and entails nucleolytic cleavage of precursor RNAs, RNA nucleotide modifications, RNA polyadenylation, RNA quality and stability control. These processes ensure proper mitochondrial RNA (mtRNA) function, and are regulated by dedicated, nuclear-encoded enzymes. Recent growing evidence suggests that mutations in these nuclear genes, leading to incorrect maturation of RNAs, are a cause of human mitochondrial disease. Additionally, mutations in mtDNA-encoded genes may also affect RNA maturation and are frequently associated with human disease. We review the current knowledge on a subset of nuclear-encoded genes coding for proteins involved in mitochondrial RNA maturation, for which genetic variants impacting upon mitochondrial pathophysiology have been reported. Also, primary pathological mtDNA mutations with recognised effects upon RNA processing are described.

No MeSH data available.


Related in: MedlinePlus

Genetic map of the mitochondrial genome. The organisation of the genes on human mitochondrial genome is shown. The two strands of the human mtDNA, denoted light (L-) and heavy (H-), code for 2 mt-rRNAs (blue), 22 mt-tRNAs (green) and 11 mt-mRNA molecules (red). The 11 mt-mRNAs encode 13 polypeptides of the electron transport chain and ATP synthase, where open reading frames of ATP8/ATP6 and ND4/ND4L overlap and are contained within bicistronic mRNAs. The main non-coding region (NCR) contains promoters for transcription of the H-strand and L-strand, HSP and LSP, respectively
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Fig1: Genetic map of the mitochondrial genome. The organisation of the genes on human mitochondrial genome is shown. The two strands of the human mtDNA, denoted light (L-) and heavy (H-), code for 2 mt-rRNAs (blue), 22 mt-tRNAs (green) and 11 mt-mRNA molecules (red). The 11 mt-mRNAs encode 13 polypeptides of the electron transport chain and ATP synthase, where open reading frames of ATP8/ATP6 and ND4/ND4L overlap and are contained within bicistronic mRNAs. The main non-coding region (NCR) contains promoters for transcription of the H-strand and L-strand, HSP and LSP, respectively

Mentions: Mitochondria are cellular compartments present in every cell of the human body (except red blood cells) and are responsible for generating almost all of the energy needed to sustain life and to grow. In mitochondria, energy is produced in the process of oxidative phosphorylation (OXPHOS). The biogenesis of the OXPHOS system entails assembly of approximately 90 proteins into five complexes. Most of these proteins are encoded by DNA that is contained within the cell nucleus (nDNA). However, 13 of these are encoded within a small, circular genome inside mitochondria (Fig. 1). Recent research has identified defects in mitochondrial DNA (mtDNA) expression that are associated with a diverse group of human disorders characterised by impaired mitochondrial respiration (Nicholls et al 2013; Boczonadi and Horvath 2014). Many regulatory factors and pathways are involved in mitochondrial gene expression and establishing the molecular details of how defects in these processes contribute to human disease constitutes a major challenge.Fig. 1


Mitochondrial transcript maturation and its disorders.

Van Haute L, Pearce SF, Powell CA, D'Souza AR, Nicholls TJ, Minczuk M - J. Inherit. Metab. Dis. (2015)

Genetic map of the mitochondrial genome. The organisation of the genes on human mitochondrial genome is shown. The two strands of the human mtDNA, denoted light (L-) and heavy (H-), code for 2 mt-rRNAs (blue), 22 mt-tRNAs (green) and 11 mt-mRNA molecules (red). The 11 mt-mRNAs encode 13 polypeptides of the electron transport chain and ATP synthase, where open reading frames of ATP8/ATP6 and ND4/ND4L overlap and are contained within bicistronic mRNAs. The main non-coding region (NCR) contains promoters for transcription of the H-strand and L-strand, HSP and LSP, respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493943&req=5

Fig1: Genetic map of the mitochondrial genome. The organisation of the genes on human mitochondrial genome is shown. The two strands of the human mtDNA, denoted light (L-) and heavy (H-), code for 2 mt-rRNAs (blue), 22 mt-tRNAs (green) and 11 mt-mRNA molecules (red). The 11 mt-mRNAs encode 13 polypeptides of the electron transport chain and ATP synthase, where open reading frames of ATP8/ATP6 and ND4/ND4L overlap and are contained within bicistronic mRNAs. The main non-coding region (NCR) contains promoters for transcription of the H-strand and L-strand, HSP and LSP, respectively
Mentions: Mitochondria are cellular compartments present in every cell of the human body (except red blood cells) and are responsible for generating almost all of the energy needed to sustain life and to grow. In mitochondria, energy is produced in the process of oxidative phosphorylation (OXPHOS). The biogenesis of the OXPHOS system entails assembly of approximately 90 proteins into five complexes. Most of these proteins are encoded by DNA that is contained within the cell nucleus (nDNA). However, 13 of these are encoded within a small, circular genome inside mitochondria (Fig. 1). Recent research has identified defects in mitochondrial DNA (mtDNA) expression that are associated with a diverse group of human disorders characterised by impaired mitochondrial respiration (Nicholls et al 2013; Boczonadi and Horvath 2014). Many regulatory factors and pathways are involved in mitochondrial gene expression and establishing the molecular details of how defects in these processes contribute to human disease constitutes a major challenge.Fig. 1

Bottom Line: Additionally, mutations in mtDNA-encoded genes may also affect RNA maturation and are frequently associated with human disease.We review the current knowledge on a subset of nuclear-encoded genes coding for proteins involved in mitochondrial RNA maturation, for which genetic variants impacting upon mitochondrial pathophysiology have been reported.Also, primary pathological mtDNA mutations with recognised effects upon RNA processing are described.

View Article: PubMed Central - PubMed

Affiliation: MRC Mitochondrial Biology Unit, Hills Road, Cambridge, CB2 0XY, UK.

ABSTRACT
Mitochondrial respiratory chain deficiencies exhibit a wide spectrum of clinical presentations owing to defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mitochondrial DNA (mtDNA) or mutations in nuclear genes coding for mitochondrially-targeted proteins. The underlying pathomechanisms can affect numerous pathways involved in mitochondrial biology including expression of mtDNA-encoded genes. Expression of the mitochondrial genes is extensively regulated at the post-transcriptional stage and entails nucleolytic cleavage of precursor RNAs, RNA nucleotide modifications, RNA polyadenylation, RNA quality and stability control. These processes ensure proper mitochondrial RNA (mtRNA) function, and are regulated by dedicated, nuclear-encoded enzymes. Recent growing evidence suggests that mutations in these nuclear genes, leading to incorrect maturation of RNAs, are a cause of human mitochondrial disease. Additionally, mutations in mtDNA-encoded genes may also affect RNA maturation and are frequently associated with human disease. We review the current knowledge on a subset of nuclear-encoded genes coding for proteins involved in mitochondrial RNA maturation, for which genetic variants impacting upon mitochondrial pathophysiology have been reported. Also, primary pathological mtDNA mutations with recognised effects upon RNA processing are described.

No MeSH data available.


Related in: MedlinePlus