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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

Primary mtDNA mutation affecting mitochondrial RNA maturation. Schematics of the “clover leaf” secondary structure of a generic mitochondrial tRNA indicating the individual positions for which mutations that affect mt-tRNA maturation are described in one or multiple mt-tRNAs (see also Table 2). The “bold circles” show mutations in mt-tRNALeu(UUR) that affect mt-rRNA maturation as well as mt-tRNA maturation
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Fig6: Primary mtDNA mutation affecting mitochondrial RNA maturation. Schematics of the “clover leaf” secondary structure of a generic mitochondrial tRNA indicating the individual positions for which mutations that affect mt-tRNA maturation are described in one or multiple mt-tRNAs (see also Table 2). The “bold circles” show mutations in mt-tRNALeu(UUR) that affect mt-rRNA maturation as well as mt-tRNA maturation

Mentions: Point mutations that interfere with mt-rRNA maturation are actually alterations in mt-tRNALeu(UUR), not in mt-rRNA itself (Fig. 6, bold circles). The common m.A3243A > G MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) mutation (King et al 1992), as well as m.3271 T > C, m.3303C > T (Koga et al 2003), m.3302A > G (Bindoff et al 1993), m.3260A > G and m.3256C > T (Rossmanith and Karwan 1998), all interfere with end processing of mt-tRNALeu(UUR) . This causes an accumulation of a precursor RNA consisting of 16S mt-rRNA linked to mt-tRNALeu(UUR) and ND1 (also known as RNA19) (Rossmanith and Karwan 1998). Although these mutations seem to interfere with 16S mt-rRNA maturation it is presumably not the crucial disease-causing molecular pathway in patients (see below, Table 2).Fig. 6


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)

Primary mtDNA mutation affecting mitochondrial RNA maturation. Schematics of the “clover leaf” secondary structure of a generic mitochondrial tRNA indicating the individual positions for which mutations that affect mt-tRNA maturation are described in one or multiple mt-tRNAs (see also Table 2). The “bold circles” show mutations in mt-tRNALeu(UUR) that affect mt-rRNA maturation as well as mt-tRNA maturation
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig6: Primary mtDNA mutation affecting mitochondrial RNA maturation. Schematics of the “clover leaf” secondary structure of a generic mitochondrial tRNA indicating the individual positions for which mutations that affect mt-tRNA maturation are described in one or multiple mt-tRNAs (see also Table 2). The “bold circles” show mutations in mt-tRNALeu(UUR) that affect mt-rRNA maturation as well as mt-tRNA maturation
Mentions: Point mutations that interfere with mt-rRNA maturation are actually alterations in mt-tRNALeu(UUR), not in mt-rRNA itself (Fig. 6, bold circles). The common m.A3243A > G MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) mutation (King et al 1992), as well as m.3271 T > C, m.3303C > T (Koga et al 2003), m.3302A > G (Bindoff et al 1993), m.3260A > G and m.3256C > T (Rossmanith and Karwan 1998), all interfere with end processing of mt-tRNALeu(UUR) . This causes an accumulation of a precursor RNA consisting of 16S mt-rRNA linked to mt-tRNALeu(UUR) and ND1 (also known as RNA19) (Rossmanith and Karwan 1998). Although these mutations seem to interfere with 16S mt-rRNA maturation it is presumably not the crucial disease-causing molecular pathway in patients (see below, Table 2).Fig. 6

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