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The Human Mitochondrial Transcriptome

T. Mercer, Shane J. Neph, M. Dinger, J. Crawford, M. Smith, Anne-Marie J. Shearwood, E. Haugen, C. Bracken, O. Rackham, J. Stamatoyannopoulos, A. Filipovska, J. Mattick
Published 2011 · Biology, Medicine

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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).
This paper references
10.1371/journal.pcbi.0020033
Identification and Classification of Conserved RNA Secondary Structures in the Human Genome
J. Pedersen (2006)
10.1101/gr.092759.109
Circos: an information aesthetic for comparative genomics.
M. Krzywinski (2009)
10.1016/j.cell.2009.06.016
Widespread Shortening of 3′UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer Cells
C. Mayr (2009)
10.4161/cc.8.11.8502
Processing mitochondrial (t)RNAs: New enzyme, old job
W. Rossmanith (2009)
10.1186/1471-2105-9-248
Dinucleotide controlled null models for comparative RNA gene prediction
T. Gesell (2008)
10.1093/nar/gkq388
Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling
I. Medina (2010)
Genome Biol
10.1038/ng.759
Chromatin accessibility pre-determines glucocorticoid receptor binding patterns
S. John (2011)
10.1093/bioinformatics/btn416
ZOOM! Zillions of oligos mapped
H. Lin (2008)
manifestation of the deafness-associated 12S rRNA 1555A>G mutation. Mitochondrion
C. Mayr (2009)
10.1128/MCB.25.15.6427-6435.2005
Polyadenylation and Degradation of Human Mitochondrial RNA: the Prokaryotic Past Leaves Its Mark
Shimyn Slomovic (2005)
10.1038/nbt.1621
Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation.
C. Trapnell (2010)
10.1093/HMG/DDG238
Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria.
R. Temperley (2003)
10.1038/nrg2683
The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs
A. Jacquier (2009)
10.1126/science.1180674
Hungry Codons Promote Frameshifting in Human Mitochondrial Ribosomes
R. Temperley (2010)
10.1093/bioinformatics/bth349
Java Treeview - extensible visualization of microarray data
A. J. Saldanha (2004)
10.1016/j.cell.2008.06.016
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
D. J. Pagliarini (2008)
10.1016/j.cell.2010.05.018
Helix Unwinding and Base Flipping Enable Human MTERF1 to Terminate Mitochondrial Transcription
E. Yakubovskaya (2010)
10.1016/j.cell.2010.06.035
PNPASE Regulates RNA Import into Mitochondria
Geng Wang (2010)
10.1261/rna.2000810
Human tRNA-derived small RNAs in the global regulation of RNA silencing.
D. Haussecker (2010)
10.1016/j.molcel.2010.06.005
Expanding the microRNA targeting code: functional sites with centered pairing.
C. Shin (2010)
10.1038/nmeth890
Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays
Peter J Sabo (2006)
10.1186/gb-2009-10-3-r25
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome
B. Langmead (2008)
10.1038/sj.ejhg.5201056
Mitochondrial A12308G polymorphism affects clinical features in patients with single mtDNA macrodeletion
M. Crimi (2003)
Identification of nuclear encoded precursor tRNAs within the mitochondrion of Trypanosoma brucei.
K. Hancock (1992)
10.1101/gr.107524.110
The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.
A. McKenna (2010)
10.1038/nbt1144
Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome
Stefan Washietl (2005)
10.1016/j.immuni.2009.08.021
CCCTC-binding factor and the transcription factor T-bet orchestrate T helper 1 cell-specific structure and function at the interferon-gamma locus.
M. Sekimata (2009)
10.1007/s00439-006-0272-4
The possible role of 10398A and 16189C mtDNA variants in providing susceptibility toT2DM in two North Indian populations: a replicative study
A. Bhat (2006)
10.18388/ABP.2006_3374
Differential stability of mitochondrial mRNA in HeLa cells.
J. Piechota (2006)
10.1038/290470A0
tRNA punctuation model of RNA processing in human mitochondria
D. Ojala (1981)
10.1080/15216540600686888
Mitochondrial DNA mutations in human disease
L. Greaves (2006)
10.1152/physrev.00025.2007
Transcriptional paradigms in mammalian mitochondrial biogenesis and function.
R. Scarpulla (2008)
10.1074/JBC.M500804200
Human Mitochondrial mRNAs Are Stabilized with Polyadenylation Regulated by Mitochondria-specific Poly(A) Polymerase and Polynucleotide Phosphorylase*
T. Nagaike (2005)
10.1016/J.MITO.2007.07.001
Nuclear-mitochondrial interaction.
G. Cannino (2007)
10.1016/0092-8674(93)90586-F
Cell
AC Tose (1993)
10.1038/nbt1417
Global identification of microRNA–target RNA pairs by parallel analysis of RNA ends
Marcelo A. German (2008)
10.1371/journal.pgen.1000474
Ancient mtDNA Genetic Variants Modulate mtDNA Transcription and Replication
S. Suissa (2009)
10.2144/000112900
Profiling the HeLa S3 transcriptome using randomly primed cDNA and massively parallel short-read sequencing.
R. Morin (2008)
10.1016/j.molcel.2009.09.028
Hierarchical rules for Argonaute loading in Drosophila.
B. Czech (2009)
10.1093/BIOINFORMATICS/BTH078
Open source clustering software
M. D. Hoon (2004)
10.1073/PNAS.95.6.2838
Structural requirements of tRNALys for its import into yeast mitochondria.
N. Entelis (1998)
10.1016/j.molcel.2010.06.001
Diverse endonucleolytic cleavage sites in the mammalian transcriptome depend upon microRNAs, Drosha, and additional nucleases.
Fedor V. Karginov (2010)
PLoS Comput. Biol
10.1128/MCB.18.10.5868
The Deafness-Associated Mitochondrial DNA Mutation at Position 7445, Which Affects tRNASer(UCN) Precursor Processing, Has Long-Range Effects on NADH Dehydrogenase Subunit ND6 Gene Expression
M. X. Guan (1998)
10.1093/NAR/1.11.1573
Internal structure of the chromatin subunit.
M. Noll (1974)
10.1016/0092-8674(87)90220-0
Promoter selection in human mitochondria involves binding of a transcription factor to orientation-independent upstream regulatory elements
R. P. Fisher (1987)
DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein.
R. P. Fisher (1992)
10.1016/j.bbabio.2010.02.036
Human mitochondrial mRNAs—like members of all families, similar but different
R. Temperley (2010)
10.1016/S0169-409X(01)00135-1
RNA delivery into mitochondria.
N. Entelis (2001)
10.1038/nature09486
The energetics of genome complexity
N. Lane (2010)
10.1038/nmeth.1313
Global mapping of protein-DNA interactions in vivo by digital genomic footprinting
J. Hesselberth (2009)
10.1016/j.molcel.2009.12.021
Mitochondrial RNA polymerase is needed for activation of the origin of light-strand DNA replication.
Javier Miralles Fusté (2010)
10.1101/gad.1837609
A novel class of small RNAs: tRNA-derived RNA fragments (tRFs).
Y. S. Lee (2009)
10.1093/NAR/13.22.8093
Length heterogeneity of a conserved displacement-loop sequence in human mitochondrial DNA.
W. Hauswirth (1985)
Human
D. Haussecker (2010)
Novel functions for small RNA molecules.
Chunxiang Zhang (2009)
10.1016/J.MITO.2007.06.004
Mammalian mitochondrial nucleoids: organizing an independently minded genome.
I. Holt (2007)
10.1080/00401706.1996.10484520
Spectral analysis for physical applications : multitaper and conventional univariate techniques
D. B. Percival (1996)
Widespread shortening of 3 0 UTRs by alternative cleavage and polyadenylation activates oncogenes in
C. Mayr (2009)
10.1073/pnas.0804283105
Mammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import
M. Rubio (2008)
10.1186/gb-2003-4-7-r44
Long mRNAs coding for yeast mitochondrial proteins of prokaryotic origin preferentially localize to the vicinity of mitochondria
J. Sylvestre (2002)
10.1101/GR.849004
WebLogo: a sequence logo generator.
G. Crooks (2004)
10.1016/S0140-6736(00)04422-6
A common mitochondrial DNA variant associated with susceptibility to dilated cardiomyopathy in two different populations
S. Khogali (2001)
10.1038/290457A0
Sequence and organization of the human mitochondrial genome
S. Anderson (1981)
10.1016/j.mito.2009.09.007
Mitochondrial haplotypes may modulate the phenotypic manifestation of the deafness-associated 12S rRNA 1555A>G mutation.
J. Lu (2010)
10.1016/0014-5793(92)80311-4
Transcription mapping of the Ori L region reveals novel precursors of mature RNA species and antisense RNAs in rat mitochondrial genome
E. Sbisà (1992)
10.1093/nar/gkp903
Human mitochondrial RNA turnover caught in flagranti: involvement of hSuv3p helicase in RNA surveillance
Roman J Szczesny (2010)
10.1128/MCB.14.12.7717
In organello footprint analysis of human mitochondrial DNA: human mitochondrial transcription factor A interactions at the origin of replication.
S. C. Ghivizzani (1994)
10.1371/journal.pbio.1001046
A User's Guide to the Encyclopedia of DNA Elements (ENCODE)
R. Myers (2011)



This paper is referenced by
10.1093/jb/mvy058
An overview of mammalian mitochondrial DNA replication mechanisms
T. Yasukawa (2018)
10.1093/nar/gks424
Mammalian NUMT insertion is non-random
J. Tsuji (2012)
10.1016/j.gene.2013.02.019
The mRNAs of maternally and paternally inherited mtDNAs of the mussel Mytilus galloprovincialis: start/end points and polycistronic transcripts.
Evanthia Chatzoglou (2013)
10.3389/fnagi.2019.00123
Humanin, a Mitochondrial-Derived Peptide Released by Astrocytes, Prevents Synapse Loss in Hippocampal Neurons
S Zárate (2019)
10.1016/j.exger.2019.03.009
Mitochondrial mRNA translation initiation contributes to oxidative metabolism in the myocardia of aged, obese mice
David E. Lee (2019)
10.3390/cells9030712
Mitochondria in the Nuclei of Rat Myocardial Cells
Chupalav M. Eldarov (2020)
RESULTS Anthropometric and Biochemical Variations in Control and T 2 D Subjects
Manjunath Ramanjaneya (2019)
10.1002/anie.201905949
Expanding APEX2 Substrates for Spatial-specific Labeling of Nucleic Acids and Proteins in Living Cells.
Ying Zhou (2019)
10.1007/978-3-319-22380-3_3
microRNAs in Mitochondria: An Unexplored Niche.
P. Borralho (2015)
10.1007/978-3-642-39426-3_4
Mitochondrial Targeting of RNA and Mitochondrial Translation
I. Tarassov (2013)
An artificial PPR scaffold for programmable RNA recognition
H. Perkins (2014)
10.1016/j.celrep.2016.07.031
Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly.
O. Rackham (2016)
10.18632/oncotarget.6129
Targeting mitochondrial RNA polymerase in acute myeloid leukemia
Fernando N. Bralha (2015)
10.1101/2020.03.02.973925
Novel Human Kidney Cell Subsets Identified by Mux-Seq
Andrew W. Schroeder (2020)
10.1016/j.semcdb.2019.10.001
Mitochondrial heteroplasmy beyond the oocyte bottleneck.
Jelle van den Ameele (2019)
10.1002/iub.2062
Involvement of PIN‐like domain nucleases in tRNA processing and translation regulation
A. Gobert (2019)
10.1007/978-94-017-8984-4_3
Regulation of Mitochondrial Function by MicroRNA
Marco Tomasetti (2014)
10.1186/s13104-020-05177-0
Functional conservation of mitochondrial RNA levels despite divergent mtDNA organization
James P. Held (2020)
10.1007/s10126-016-9719-3
Identification of Mitochondrial Genome-Encoded Small RNAs Related to Egg Deterioration Caused by Postovulatory Aging in Rainbow Trout
H. Ma (2016)
10.1186/s12864-017-4080-0
Variation and evolution of polyadenylation profiles in sauropsid mitochondrial mRNAs as deduced from the high-throughput RNA sequencing
Yao Sun (2017)
10.1002/ange.201905949
Expanding APEX2 Substrates for Spatial‐specific Labeling of Nucleic Acids and Proteins in Living Cells
Ying Zhou (2019)
10.1016/j.ebiom.2019.09.015
Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's disease
P. Podlesniy (2019)
10.1038/nature14546
Metabolic rescue in pluripotent cells from patients with mtDNA disease
H. Ma (2015)
10.1111/1744-7917.12463
The evolutionary development of plant‐feeding insects and their nutritional endosymbionts
I. H. Skidmore (2017)
10.1093/hmg/ddx142
Evidence of nuclei‐encoded spliceosome mediating splicing of mitochondrial RNA
R. Herai (2017)
10.18632/oncotarget.11719
The mitochondrial translation machinery as a therapeutic target in Myc-driven lymphomas
Aleco D'Andrea (2016)
10.1101/2020.03.10.985606
Variability in mitochondrial import, mitochondrial health and mtDNA copy number using Type II and Type V CRISPR effectors
Zuriñe Antón (2020)
10.1093/eep/dvw020
Maternal smoking during pregnancy is associated with mitochondrial DNA methylation
D. Armstrong (2016)
10.1155/2017/2309034
Mitochondrial (Dys) Function in Inflammaging: Do MitomiRs Influence the Energetic, Oxidative, and Inflammatory Status of Senescent Cells?
A. Giuliani (2017)
10.1038/s41418-019-0374-x
Deletion of heat shock protein 60 in adult mouse cardiomyocytes perturbs mitochondrial protein homeostasis and causes heart failure
F. Fan (2019)
10.1530/JME-12-0203
The emerging role of the mitochondrial-derived peptide humanin in stress resistance.
K. Yen (2013)
10.1016/j.ymeth.2017.05.017
CeFra-seq: Systematic mapping of RNA subcellular distribution properties through cell fractionation coupled to deep-sequencing.
F. A. Lefebvre (2017)
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