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Mitochondrial transcript maturation and its disorders

Lookup NU author(s): Dr Thomas NichollsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Van Haute L, Pearce SF, Powell CA, D'Souza AR, Nicholls TJ, Minczuk M

Publication type: Review

Publication status: Published

Journal: Journal of Inherited Metabolic Disease

Year: 2015

Volume: 38

Issue: 4

Pages: 655-680

Print publication date: 01/07/2015

Online publication date: 28/05/2015

Acceptance date: 29/04/2015

ISSN (print): 0141-8955

ISSN (electronic): 1573-2665


DOI: 10.1007/s10545-015-9859-z

PubMed id: 26016801