Mitochondrial transcript maturation and its disorders.

TitleMitochondrial transcript maturation and its disorders.
Publication TypeJournal Article
Year of Publication2015
AuthorsVan Haute, L, Pearce, SF, Powell, CA, D'Souza, AR, Nicholls, TJ, Minczuk, M
JournalJ Inherit Metab Dis
Date Published2015 Jul
KeywordsDNA, Mitochondrial, Humans, Mitochondria, Mitochondrial Diseases, RNA

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.

Alternate JournalJ. Inherit. Metab. Dis.
Citation Key10.1007/s10545-015-9859-z
PubMed ID26016801
PubMed Central IDPMC4493943
Grant ListMC_U105697135 / / Medical Research Council / United Kingdom