The Human Mitochondrial Transcriptome
Open accessAbstract
The human mitochondrial genome comprises a distinct genetic system transcribed as precursor polycistronic transcripts that are subsequently cleaved to generate individual mRNAs, tRNAs, and rRNAs. Here, we provide a comprehensive analysis of the human mitochondrial transcriptome across multiple cell lines and tissues. Using directional deep sequencing and parallel analysis of RNA ends, we demonstrate wide variation in mitochondrial transcript abundance and precisely resolve transcript processing and maturation events. We identify previously undescribed transcripts, including small RNAs, and observe the enrichment of several nuclear RNAs in mitochondria. Using high-throughput in vivo DNaseI footprinting, we establish the global profile of DNA-binding protein occupancy across the mitochondrial genome at single-nucleotide resolution, revealing regulatory features at mitochondrial transcription initiation sites and functional insights into disease-associated variants. This integrated analysis of the mitochondrial transcriptome reveals unexpected complexity in the regulation, expression, and processing of mitochondrial RNA and provides a resource for future studies of mitochondrial function (accessed at http://mitochondria.matticklab.com).
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In the heart, 30% of total messenger RNA molecules are of mitochondrial origin, whereas ~5% of total messenger RNA load in leukocytes is encoded by mitochondrial genes.
“In the heart, 30% of the total messenger RNA molecules are of mitochondrial origin, whereas ~5% of the total messenger RNA load in less metabolically active cells such as leukocytes is encoded by mitochondrial genes (39).”
From Autoantibodies in Systemic Lupus Erythematosus Target Mitochondrial RNA (2019) · cites this paper as [39]
The Results section (“Mitochondrial gene expression”) says mitochondrial transcripts comprise almost 30% of total mRNA in the heart. It includes white blood cells among lower-energy-demand tissues for which mitochondrial transcripts contribute a lower bound of approximately 5%; the claim omits that lower-bound qualification. (LLM, conf=0.86)
Experimental — accuracy not yet measuredWithin mitochondria, mtDNA is transcribed into polycistronic RNAs and processed into mature mtRNA.
“within the mitochondrion, mtDNA is transcribed into polycistronic RNAs and then processed into mature mtRNA22,23.”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [22]
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- Authors
- Mercer, T. R., Neph, S., Dinger, M. E., Crawford, J., Smith, M. A., Shearwood, A.-M. J., Haugen, E., Bracken, C. P., Rackham, O., Stamatoyannopoulos, J. A., Filipovska, A., & Mattick, J. S.
- Affiliations
- The University of Queensland (AU)
- University of Washington (US)
- The University of Western Australia (AU)
- South Australia Pathology (AU)
- Corresponding author
- Stamatoyannopoulos, John A.
- Filipovska, Aleksandra
- Mattick, John S.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 146
- Issue
- 4
- Pages
- 645-658
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3160626
- OpenAlex
- W2170819005
- Cited by
- 905
- References
- 67
- Citations by year
- 2026: 48 · 2025: 49 · 2024: 98 · 2023: 62 · 2022: 75 · 2021: 68 · 2020: 72 · 2019: 75 · 2018: 63 · 2017: 60 · 2016: 47 · 2015: 57 · 2014: 45 · 2013: 43 · 2012: 28
- FWCI
- 16.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 716 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- Australian Government
- Queensland Government
- National Institutes of Health
- Australian Research Council
- National Health and Medical Research Council
- National Human Genome Research Institute (U54HG004592, U54HG004592-S1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- human mitochondrial genome, mitochondrial transcriptome, polycistronic transcripts, mitochondrial RNA processing, tRNA, ribosomal RNA, small RNA, DNase I footprinting, disease-associated variants
- MeSH terms
- RNA, Mitochondrial, Cell Nucleus, Deoxyribonuclease I, DNA-Binding Proteins, Gene Expression Regulation, Humans, Mitochondria, Nucleic Acid Conformation, RNA, Sequence Analysis, RNA, DNA Footprinting, Locus Control Region, Gene Expression Profiling, Mitochondrial Proteins, Genome, Mitochondrial, High-Throughput Nucleotide Sequencing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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