Fidelity of translation initiation is required for coordinated respiratory complex assembly

被引:50
作者
Rudler, Danielle L. [1 ,2 ]
Hughes, Laetitia A. [1 ,2 ]
Perks, Kara L. [1 ,2 ]
Richman, Tara R. [1 ,2 ]
Kuznetsova, Irina [1 ,2 ]
Ermer, Judith A. [1 ,2 ]
Abudulai, Laila N. [3 ,4 ]
Shearwood, Anne-Marie J. [1 ,2 ]
Viola, Helena M. [5 ]
Hool, Livia C. [5 ,6 ]
Siira, Stefan J. [1 ,2 ]
Rackham, Oliver [1 ,7 ,8 ]
Filipovska, Aleksandra [1 ,2 ,9 ]
机构
[1] QEII Med Ctr, Harry Perkins Inst Med Res, Nedlands, WA 6009, Australia
[2] Univ Western Australia, Ctr Med Res, QEII Med Ctr, Nedlands, WA 6009, Australia
[3] Univ Western Australia, Ctr Microscopy Characterisat & Anal, Crawley, WA 6009, Australia
[4] Univ Western Australia, Sch Biomed Sci, Crawley, WA 6009, Australia
[5] Univ Western Australia, Sch Human Sci Physiol, Crawley, WA 6009, Australia
[6] Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia
[7] Curtin Univ, Sch Pharm & Biomed Sci, Bentley, WA 6102, Australia
[8] Curtin Univ, Curtin Hlth Innovat Res Inst, Bentley, WA, Australia
[9] Univ Western Australia, Sch Mol Sci, Crawley, WA 6009, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
MITOCHONDRIAL RIBOSOME; RECYCLING FACTOR; IN-VIVO; RNA; LRPPRC; DOMAIN; IDENTIFICATION; STABILITY; PROTEINS; SUBUNIT;
D O I
10.1126/sciadv.aay2118
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-tRNA(Met), 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-tRNA(Met) 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.
引用
收藏
页数:15
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