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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

Mitochondrial RNA metabolism. The mitochondrial rRNAs (blue), mRNAs (red) and tRNAs (green) are transcribed from the L- and H-strands as polycistronic units that undergo endonucleolytic processing. Following the liberation of the individual mt-mRNA, mt-rRNA and mt-tRNA transcripts, they undergo post-transcriptional modifications. Several nucleotides of mt-rRNAs are modified to facilitate mitoribosome biogenesis and function. A poly(A) tail is added to mt-mRNAs, with the exception of the L-strand-encoded ND6. Mt-tRNAs undergo extensive post-transcriptional nucleotide modification, in addition to a CCA trinucleotide synthesis at the 3′ end, before being aminoacylated with a cognate amino acid. Decay and surveillance pathways have also been described for mammalian mtRNA
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Fig2: Mitochondrial RNA metabolism. The mitochondrial rRNAs (blue), mRNAs (red) and tRNAs (green) are transcribed from the L- and H-strands as polycistronic units that undergo endonucleolytic processing. Following the liberation of the individual mt-mRNA, mt-rRNA and mt-tRNA transcripts, they undergo post-transcriptional modifications. Several nucleotides of mt-rRNAs are modified to facilitate mitoribosome biogenesis and function. A poly(A) tail is added to mt-mRNAs, with the exception of the L-strand-encoded ND6. Mt-tRNAs undergo extensive post-transcriptional nucleotide modification, in addition to a CCA trinucleotide synthesis at the 3′ end, before being aminoacylated with a cognate amino acid. Decay and surveillance pathways have also been described for mammalian mtRNA

Mentions: The generation of functional RNA molecules used for protein synthesis requires transcription, nucleolytic processing, post-transcriptional nucleotide modifications, polyadenylation of mt-mRNA and mt-tRNA-aminoacylation (Fig. 2). These steps are coordinated with RNA quality control, RNA stability regulation, biogenesis of the mitochondrial ribosome and translation activation (Fig. 2). However, the mechanistic details of how these processes occur are still unknown. In the first part of the review, before discussing human diseases associated with defects of mitochondrial RNA metabolism, we summarise the current available data on mtRNA metabolism.Fig. 2


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)

Mitochondrial RNA metabolism. The mitochondrial rRNAs (blue), mRNAs (red) and tRNAs (green) are transcribed from the L- and H-strands as polycistronic units that undergo endonucleolytic processing. Following the liberation of the individual mt-mRNA, mt-rRNA and mt-tRNA transcripts, they undergo post-transcriptional modifications. Several nucleotides of mt-rRNAs are modified to facilitate mitoribosome biogenesis and function. A poly(A) tail is added to mt-mRNAs, with the exception of the L-strand-encoded ND6. Mt-tRNAs undergo extensive post-transcriptional nucleotide modification, in addition to a CCA trinucleotide synthesis at the 3′ end, before being aminoacylated with a cognate amino acid. Decay and surveillance pathways have also been described for mammalian mtRNA
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Mitochondrial RNA metabolism. The mitochondrial rRNAs (blue), mRNAs (red) and tRNAs (green) are transcribed from the L- and H-strands as polycistronic units that undergo endonucleolytic processing. Following the liberation of the individual mt-mRNA, mt-rRNA and mt-tRNA transcripts, they undergo post-transcriptional modifications. Several nucleotides of mt-rRNAs are modified to facilitate mitoribosome biogenesis and function. A poly(A) tail is added to mt-mRNAs, with the exception of the L-strand-encoded ND6. Mt-tRNAs undergo extensive post-transcriptional nucleotide modification, in addition to a CCA trinucleotide synthesis at the 3′ end, before being aminoacylated with a cognate amino acid. Decay and surveillance pathways have also been described for mammalian mtRNA
Mentions: The generation of functional RNA molecules used for protein synthesis requires transcription, nucleolytic processing, post-transcriptional nucleotide modifications, polyadenylation of mt-mRNA and mt-tRNA-aminoacylation (Fig. 2). These steps are coordinated with RNA quality control, RNA stability regulation, biogenesis of the mitochondrial ribosome and translation activation (Fig. 2). However, the mechanistic details of how these processes occur are still unknown. In the first part of the review, before discussing human diseases associated with defects of mitochondrial RNA metabolism, we summarise the current available data on mtRNA metabolism.Fig. 2

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