The human mitochondrial transcript ... | Article | H1 Connect

In the 30 years since mitochondrial DNA (mtDNA) became the first human genome to be sequenced, considerable progress has been made in understanding how its two strands are transcribed as single transcripts and processed into individual mRNAs, ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs). This is the first study to apply massively parallel sequencing to determine the composition of the human mitochondrial transcriptome, and demonstrates several examples of unexpected complexity. These included the presence of significant amounts of stable antisense RNAs, highly expressed small RNAs that are mostly derived from tRNA genes, and validation that several processed nuclear-encoded tRNAs were truly present inside mitochondria rather than contaminants. The authors demonstrate marked differences in the abundance of specific RNAs in different cell lines and refine knowledge of RNA processing sites. They also used DNaseI footprinting to identify putative protein-DNA interaction sites representing ~8% of the mtDNA genome. Sequence variants in a number of these sites have been associated with disease. Overall, the study provides a wealth of data and resources for future studies on the expression of the mtDNA genome in health and disease.