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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

Post-transcriptional modifications of mitochondrial transfer RNA and human disease. Schematics of the “clover leaf” secondary structure of a generic mitochondrial tRNA indicating post-transcriptionally modified bases (circles) is shown. The details of the chemical modification and the enzyme responsible (if known) for each mt-tRNA position is given in boxes, indicating the mt-tRNA base position number next to each box. The chemical modifications identified in mammalian species other than human are in brackets. Colour coding: red, enzyme responsible for the modification has been associated with human disease; blue, enzyme responsible for particular modification has been identified; grey, modifying enzyme has not been identified
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Fig5: Post-transcriptional modifications of mitochondrial transfer RNA and human disease. Schematics of the “clover leaf” secondary structure of a generic mitochondrial tRNA indicating post-transcriptionally modified bases (circles) is shown. The details of the chemical modification and the enzyme responsible (if known) for each mt-tRNA position is given in boxes, indicating the mt-tRNA base position number next to each box. The chemical modifications identified in mammalian species other than human are in brackets. Colour coding: red, enzyme responsible for the modification has been associated with human disease; blue, enzyme responsible for particular modification has been identified; grey, modifying enzyme has not been identified

Mentions: A complete set of modifications for bovine mt-tRNAs, which share a high degree of structural and sequence similarity with human mt-tRNAs, have recently been described (Suzuki and Suzuki 2014). From this work, many human mt-tRNA modifying enzymes may be predicted, bringing us closer to a comprehensive modification profile for human mt-tRNAs (current status summarised in Fig. 5, expanded upon in Powell et al (2015) and Suzuki et al (2011).Fig. 5


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)

Post-transcriptional modifications of mitochondrial transfer RNA and human disease. Schematics of the “clover leaf” secondary structure of a generic mitochondrial tRNA indicating post-transcriptionally modified bases (circles) is shown. The details of the chemical modification and the enzyme responsible (if known) for each mt-tRNA position is given in boxes, indicating the mt-tRNA base position number next to each box. The chemical modifications identified in mammalian species other than human are in brackets. Colour coding: red, enzyme responsible for the modification has been associated with human disease; blue, enzyme responsible for particular modification has been identified; grey, modifying enzyme has not been identified
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493943&req=5

Fig5: Post-transcriptional modifications of mitochondrial transfer RNA and human disease. Schematics of the “clover leaf” secondary structure of a generic mitochondrial tRNA indicating post-transcriptionally modified bases (circles) is shown. The details of the chemical modification and the enzyme responsible (if known) for each mt-tRNA position is given in boxes, indicating the mt-tRNA base position number next to each box. The chemical modifications identified in mammalian species other than human are in brackets. Colour coding: red, enzyme responsible for the modification has been associated with human disease; blue, enzyme responsible for particular modification has been identified; grey, modifying enzyme has not been identified
Mentions: A complete set of modifications for bovine mt-tRNAs, which share a high degree of structural and sequence similarity with human mt-tRNAs, have recently been described (Suzuki and Suzuki 2014). From this work, many human mt-tRNA modifying enzymes may be predicted, bringing us closer to a comprehensive modification profile for human mt-tRNAs (current status summarised in Fig. 5, expanded upon in Powell et al (2015) and Suzuki et al (2011).Fig. 5

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