Abstract
Human mitochondrial ribosomes are specialized in the synthesis of 13 proteins, which are fundamental components of the oxidative phosphorylation system. The pathway of mitoribosome biogenesis, the compartmentalization of the process, and factors involved remain largely unknown. Here, we have identified the DEAD-box protein DDX28 as an RNA granule component essential for the biogenesis of the mitoribosome large subunit (mt-LSU). DDX28 interacts with the 16S rRNA and the mt-LSU. RNAi-mediated DDX28 silencing in HEK293T cells does not affect mitochondrial mRNA stability or 16S rRNA processing or modification. However, it leads to reduced levels of 16S rRNA and mt-LSU proteins, impaired mt-LSU assembly, deeply attenuated mitochondrial protein synthesis, and consequent failure to assemble oxidative phosphorylation complexes. Our findings identify DDX28 as essential during the early stages of mitoribosome mt-LSU biogenesis, a process that takes place mainly near the mitochondrial nucleoids, in the compartment defined by the RNA granules.
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•DDX28 is a DEAD-box protein essential for mitoribosome LSU (mt-LSU) assembly•DDX28 interacts with the 16S rRNA and the mt-LSU•The helicase activity of DDX28 is required for its function•DDX28 locates to the RNA granules, where mitoribosome assembly occurs
Mitoribosomal biogenesis and the factors involved are poorly characterized. Tu and Barrientos now show that the human DEAD-box protein DDX28 plays an essential role during the early stages of mitoribosome large-subunit assembly by interacting with the 16S rRNA. DDX28 is a component of the RNA granule, where mitoribosome assembly is accomplished.
