Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit.

TitleHuman C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit.
Publication TypeJournal Article
Year of Publication2012
AuthorsHe, J, Cooper, HM, Reyes, A, Di Re, M, Kazak, L, Wood, SR, Mao, CC, Fearnley, IM, Walker, JE, Holt, IJ
JournalNucleic Acids Res
Volume40
Issue13
Pagination6097-108
Date Published2012 Jul
ISSN1362-4962
KeywordsCell Line, Tumor, DNA, Mitochondrial, GTP Phosphohydrolases, Guanosine Triphosphate, HEK293 Cells, Humans, Mitochondria, Ribosome Subunits, Small, Eukaryotic
Abstract

The bacterial homologue of C4orf14, YqeH, has been linked to assembly of the small ribosomal subunit. Here, recombinant C4orf14 isolated from human cells, co-purified with the small, 28S subunit of the mitochondrial ribosome and the endogenous protein co-fractionated with the 28S subunit in sucrose gradients. Gene silencing of C4orf14 specifically affected components of the small subunit, leading to decreased protein synthesis in the organelle. The GTPase of C4orf14 was critical to its interaction with the 28S subunit, as was GTP. Therefore, we propose that C4orf14, with bound GTP, binds to components of the 28S subunit facilitating its assembly, and GTP hydrolysis acts as the release mechanism. C4orf14 was also found to be associated with human mitochondrial nucleoids, and C4orf14 gene silencing caused mitochondrial DNA depletion. In vitro C4orf14 is capable of binding to DNA. The association of C4orf14 with mitochondrial translation factors and the mitochondrial nucleoid suggests that the 28S subunit is assembled at the mitochondrial nucleoid, enabling the direct transfer of messenger RNA from the nucleoid to the ribosome in the organelle.

DOI10.1093/nar/gks257
Alternate JournalNucleic Acids Res.
Citation Key10.1093/nar/gks257
PubMed ID22447445
PubMed Central IDPMC3401442
Grant ListBB/F012802/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_U105663140 / / Medical Research Council / United Kingdom
MC_U105663148 / / Medical Research Council / United Kingdom