Download Mitochondrial transcript processing and its disorders

Mitochondrial transcript processing and its disorders
Michal Minczuk, PhD
MRC Mitochondrial Biology Unit, Cambridge UK
Mitochondrial respiratory chain deficiencies exhibit a wide spectrum of clinical
presentations. These pathologies result from defective mitochondrial energy
production and 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. Recent
studies have revealed that expression of the mitochondrial genes is extensively
regulated at the post-transcriptional stages that entail 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 frequent cause of human mitochondrial disease. I will
discuss the current knowledge and most recent discoveries related to 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.