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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 ribosomal RNA. Schematics of the secondary structure of 12S and 16S mt-rRNAs, indicating post-transcriptionally modified bases (circles) is shown. The details of the chemical modification and enzyme responsible (if known) for each mt-rRNA position is given in boxes, indicating the mt-rRNA base position number next to each box. The chemical modifications identified in mammalian species other than human are in brackets. Colour coding: blue, enzyme responsible for particular modification has been identified; grey, modifying enzyme has not been identified
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Fig4: Post-transcriptional modifications of mitochondrial ribosomal RNA. Schematics of the secondary structure of 12S and 16S mt-rRNAs, indicating post-transcriptionally modified bases (circles) is shown. The details of the chemical modification and enzyme responsible (if known) for each mt-rRNA position is given in boxes, indicating the mt-rRNA base position number next to each box. The chemical modifications identified in mammalian species other than human are in brackets. Colour coding: blue, enzyme responsible for particular modification has been identified; grey, modifying enzyme has not been identified

Mentions: Mt-tRNA cleavage from the mitochondrial H-strand precursor liberates full-length 12S and 16S mt-rRNAs without a requirement of any further nucleolytic processing events. Five nucleotide modifications have been identified in the mammalian 12S mt-rRNA, with one methylated uracil (12S: m5U429, mtDNA position: 1076), two cytosine methylations (12S: m4C839 and m5C841, mtDNA positions: 1486 and 1488, respectively) and two dimethylated adenosines (12S: m62A936 and m62A937, mtDNA positions: 1583 and 1584) (Baer and Dubin 1981). Only two of the proteins responsible for these post-transcriptional nucleotide modifications have been characterised to date (Fig. 4).Fig. 4


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 ribosomal RNA. Schematics of the secondary structure of 12S and 16S mt-rRNAs, indicating post-transcriptionally modified bases (circles) is shown. The details of the chemical modification and enzyme responsible (if known) for each mt-rRNA position is given in boxes, indicating the mt-rRNA base position number next to each box. The chemical modifications identified in mammalian species other than human are in brackets. Colour coding: blue, enzyme responsible for particular modification has been identified; grey, modifying enzyme has not been identified
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Post-transcriptional modifications of mitochondrial ribosomal RNA. Schematics of the secondary structure of 12S and 16S mt-rRNAs, indicating post-transcriptionally modified bases (circles) is shown. The details of the chemical modification and enzyme responsible (if known) for each mt-rRNA position is given in boxes, indicating the mt-rRNA base position number next to each box. The chemical modifications identified in mammalian species other than human are in brackets. Colour coding: blue, enzyme responsible for particular modification has been identified; grey, modifying enzyme has not been identified
Mentions: Mt-tRNA cleavage from the mitochondrial H-strand precursor liberates full-length 12S and 16S mt-rRNAs without a requirement of any further nucleolytic processing events. Five nucleotide modifications have been identified in the mammalian 12S mt-rRNA, with one methylated uracil (12S: m5U429, mtDNA position: 1076), two cytosine methylations (12S: m4C839 and m5C841, mtDNA positions: 1486 and 1488, respectively) and two dimethylated adenosines (12S: m62A936 and m62A937, mtDNA positions: 1583 and 1584) (Baer and Dubin 1981). Only two of the proteins responsible for these post-transcriptional nucleotide modifications have been characterised to date (Fig. 4).Fig. 4

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