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@ARTICLE{Remes:1007362,
author = {Remes, Cristina and Khawaja, Anas and Pearce, Sarah F and
Dinan, Adam M and Gopalakrishna, Shreekara and Cipullo,
Miriam and Kyriakidis, Vasileios and Zhang, Jingdian and
Dopico, Xaquin Castro and Yukhnovets, Olessya and Atanassov,
Ilian and Firth, Andrew E and Cooperman, Barry and Rorbach,
Joanna},
title = {{T}ranslation initiation of leaderless and polycistronic
transcripts in mammalian mitochondria},
journal = {Nucleic acids research},
volume = {51},
number = {2},
issn = {0305-1048},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {FZJ-2023-02031},
pages = {891 - 907},
year = {2023},
abstract = {The synthesis of mitochondrial OXPHOS complexes is central
to cellular metabolism, yet many molecular details of
mitochondrial translation remain elusive. It has been
commonly held view that translation initiation in human
mitochondria proceeded in a manner similar to bacterial
systems, with the mitoribosomal small subunit bound to the
initiation factors, mtIF2 and mtIF3, along with initiator
tRNA and an mRNA. However, unlike in bacteria, most human
mitochondrial mRNAs lack 5′ leader sequences that can
mediate small subunit binding, raising the question of how
leaderless mRNAs are recognized by mitoribosomes. By using
novel in vitro mitochondrial translation initiation assays,
alongside biochemical and genetic characterization of
cellular knockouts of mitochondrial translation factors, we
describe unique features of translation initiation in human
mitochondria. We show that in vitro, leaderless mRNA
transcripts can be loaded directly onto assembled 55S
mitoribosomes, but not onto the mitoribosomal small subunit
(28S), in a manner that requires initiator fMet-tRNAMet
binding. In addition, we demonstrate that in human cells and
in vitro, mtIF3 activity is not required for translation of
leaderless mitochondrial transcripts but is essential for
translation of ATP6 in the case of the bicistronic ATP8/ATP6
transcript. Furthermore, we show that mtIF2 is indispensable
for mitochondrial protein synthesis. Our results demonstrate
an important evolutionary divergence of the mitochondrial
translation system and further our fundamental understanding
of a process central to eukaryotic metabolism.},
cin = {IBI-6},
ddc = {570},
cid = {I:(DE-Juel1)IBI-6-20200312},
pnm = {5352 - Understanding the Functionality of Soft Matter and
Biomolecular Systems (POF4-535)},
pid = {G:(DE-HGF)POF4-5352},
typ = {PUB:(DE-HGF)16},
pubmed = {36629253},
UT = {WOS:000910085600001},
doi = {10.1093/nar/gkac1233},
url = {https://juser.fz-juelich.de/record/1007362},
}