Rudler, Danielle L. and Hughes, Laetitia A. and Perks, Kara L. and Richman, Tara R. and Kuznetsova, Irina and Ermer, Judith A. and Abudulai, Laila N. and Shearwood, Anne-Marie J. and Viola, Helena M. and Hool, Livia C. and Siira, Stefan J. and Rackham, Oliver and Filipovska, Aleksandra (2019) Fidelity of translation initiation is required for coordinated respiratory complex assembly. Science Advances, 5 (12). pp. eaay2118. ISSN 2375-2548
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Abstract
Mammalian mitochondrial ribosomes are unique molecular machines that translate 11 leaderless mRNAs; however, it is not clear how mitoribosomes initiate translation, since mitochondrial mRNAs lack untranslated regions. Mitochondrial translation initiation shares similarities with prokaryotes, 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, which closes the decoding center and stabilizes the binding of the fMet-tRNAMet to the leaderless mRNAs, and MTIF3, whose role is not clear. We show that MTIF3 is essential for survival and that heart- and skeletal muscle-specific loss of MTIF3 causes cardiomyopathy. We identify increased but uncoordinated mitochondrial protein synthesis in mice lacking MTIF3, resulting in loss of specific respiratory complexes. Ribosome profiling shows that MTIF3 is required for recognition and regulation of translation initiation of mitochondrial mRNAs and for coordinated assembly of OXPHOS complexes in vivo.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 23 Jan 2020 04:42 |
| Last Modified: | 30 Jul 2020 00:22 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/920 |
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