title: The human mitochondrial transcriptome.
abstract: 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).
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Mercer
authors.forename: Shane
authors.initials: S
authors.lastname: Neph
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Dinger
authors.forename: Joanna
authors.initials: J
authors.lastname: Crawford
authors.forename: Martin A
authors.initials: MA
authors.lastname: Smith
authors.forename: Anne-Marie J
authors.initials: AM
authors.lastname: Shearwood
authors.forename: Eric
authors.initials: E
authors.lastname: Haugen
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Bracken
authors.forename: Oliver
authors.initials: O
authors.lastname: Rackham
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Filipovska
authors.forename: John S
authors.initials: JS
authors.lastname: Mattick
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000032:analysis; D003850:Deoxyribonuclease I / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054629:Genome, Mitochondrial; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D019901:Locus Control Region; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000032:analysis; D009690:Nucleic Acid Conformation; D012313:RNA / Q000032:analysis* / Q000378:metabolism; D000077278:RNA, Mitochondrial; D017423:Sequence Analysis, RNA
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D000077278:RNA, Mitochondrial; D012313:RNA; D003850:Deoxyribonuclease I