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Series GSE131154 Query DataSets for GSE131154
Status Public on Jan 13, 2020
Title Fidelity of translation initiation is required for coordinated respiratory complex assembly
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Mammalian mitochondrial ribosomes are unique molecular machines that translate 11 leaderless mRNAs. To date it is not clear how mitoribosomes recognize and initiate translation in the absence of untranslated regions in the mitochondrial mRNAs. Translation initiation in mitochondria shares similarities with prokaryotic systems, such as the formation of a ternary complex of fMet-tRNAMet, mRNA and the 28S subunit, but differs in the requirements for initiation factors. Mitochondria have two initiation factors, MTIF2 that closes the decoding centre and stabilizes the binding of the fMet-tRNAMet to the leaderless mRNAs, and MTIF3 whose role is not clear. We knocked out Mtif3 in mice and show that this protein is essential for embryo development and heart- and skeletal muscle-specific loss of MTIF3 causes premature death. We identify increased but uncoordinated mitochondrial protein synthesis in mice lacking MTIF3 that results in loss of specific respiratory complexes. Therefore, we show that coordinated assembly of OXPHOS complexes requires stoichiometric levels of nuclear and mitochondrially-encoded protein subunits in vivo. Our ribosome profiling and transcriptomic analyses show that MTIF3 is required for recognition and regulation of translation initiation of mitochondrial mRNAs, but not dissociation of the ribosome subunits.
Overall design Total RNA was isolated from heart tissue from 25 week old control (Mtif3loxP/loxP) and Mtif3 knockout mice (Mtif3loxP/loxP, +/Ckmm), and TruSeq libraries produced, sequenced and analysed for differential expression. Sucrose gradient fractions of mitochondrial RNA corresponding to small and large subunit, as well as assembled ribosomes, was isolated from heart tissue from 25 week old control (Mtif3loxP/loxP) and Mtif3 knockout mice (Mtif3loxP/loxP, +/Ckmm), and ribosome profiling libraries produced and sequenced.
Contributor(s) Rudler DL, Hughes L, Perks KL, Richman T, Kuznetsova I, Ermer JA, Abudulai LN, Shearwood AJ, Viola HM, Hool LC, Siira SJ, Rackham O, Filipovska A
Citation(s) 31903419
Submission date May 13, 2019
Last update date Jan 13, 2020
Contact name Stefan J Siira
Organization name Harry Perkins Institute of Medical Research
Department Molecular medicine
Lab Mitochondrial medicine and biology
Street address 6 Verdun St, Nedlands
City Perth
State/province Western Australia
ZIP/Postal code 6009
Country Australia
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (8)
GSM3764756 Ribo_F7_WT
GSM3764757 Ribo_F9_WT
GSM3764758 Ribo_F11_WT
BioProject PRJNA542722
SRA SRP198313

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Supplementary file Size Download File type/resource
GSE131154_RAW.tar 1010.0 Kb (http)(custom) TAR (of BED, WIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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