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

Published version
Peer-reviewed

Type

Article

Change log

Authors

He, J 
Cooper, HM 
Reyes, A 
Di Re, M 
Kazak, L 

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.

Description

Keywords

Cell Line, Tumor, DNA, Mitochondrial, GTP Phosphohydrolases, Guanosine Triphosphate, HEK293 Cells, Humans, Mitochondria, Ribosome Subunits, Small, Eukaryotic

Journal Title

Nucleic Acids Research

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

40

Publisher

Oxford University Press
Sponsorship
Medical Research Council (MC_U105663148)
Medical Research Council (MRC); Biotechnology and Biological Sciences Research Council (BBSRC); European Union; Academy of Finland (to H.M.C.). Funding for open access charge: MRC.