PXD015521

PXD015521 is an original dataset announced via ProteomeXchange.

Title	Fidelity of translation initiation is required for coordinated respiratory complex assembly
Description	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.
HostingRepository	PRIDE
AnnounceDate	2020-01-13
AnnouncementXML	Submission_2020-01-17_05:55:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Irina Kuznetsova
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-20 01:26:53	ID requested
1	2020-01-13 04:41:42	announced
⏵ 2	2020-01-17 05:55:11	announced	2020-01-17: Updated publication reference for PubMed record(s): 31903419.

Rudler DL, Hughes LA, Perks KL, Richman TR, Kuznetsova I, Ermer JA, Abudulai LN, Shearwood AJ, Viola HM, Hool LC, Siira SJ, Rackham O, Filipovska A, Fidelity of translation initiation is required for coordinated respiratory complex assembly. Sci Adv, 5(12):eaay2118(2019) [pubmed]

submitter keyword: translation, cardiomyopathy, ribosome, RNA-Seq

Aleksandra Filipovska
contact affiliation	-Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia 6009, Australia -Centre for Medical Research, The University of Western Australia, QEII Medical Centre, Nedlands, Western Australia 6009, Australia -School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia 6009, Australia
contact email	aleksandra.filipovska@uwa.edu.au
lab head
Irina Kuznetsova
contact affiliation	UWA
contact email	irina.kuznetsova@perkins.org.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/01/PXD015521

PRIDE project URI

• PRIDE
  1. PXD015521
     1. Label: PRIDE project
     2. Name: Fidelity of translation initiation is required for coordinated respiratory complex assembly