Dual function of GTPBP6 in biogenesis and recycling of human mitochondrial ribosomes.

Elena Lavdovskaia,Marina V Rodnina,Henning Urlaub,Emely Steube,Andreas Linden,Kärt Denks,Ricarda Richter-Dennerlein,Franziska Nadler

doi:10.1093/nar/gkaa1132

Abstract

Translation and ribosome biogenesis in mitochondria require auxiliary factors that ensure rapid and accurate synthesis of mitochondrial proteins. Defects in translation are associated with oxidative phosphorylation deficiency and cause severe human diseases, but the exact roles of mitochondrial translation-associated factors are not known. Here we identify the functions of GTPBP6, a homolog of the bacterial ribosome-recycling factor HflX, in human mitochondria. Similarly to HflX, GTPBP6 facilitates the dissociation of ribosomes in vitro and in vivo. In contrast to HflX, GTPBP6 is also required for the assembly of mitochondrial ribosomes. GTPBP6 ablation leads to accumulation of late assembly intermediate(s) of the large ribosomal subunit containing ribosome biogenesis factors MTERF4, NSUN4, MALSU1 and the GTPases GTPBP5, GTPBP7 and GTPBP10. Our data show that GTPBP6 has a dual function acting in ribosome recycling and biogenesis. These findings contribute to our understanding of large ribosomal subunit assembly as well as ribosome recycling pathway in mitochondria.

Highlights

The biogenesis and the function of the mitochondrial ribosome is of central importance for the fitness and viability of eukaryotic cells, and mutations in genes encoding for mitochondrial ribosomal proteins or translation factors lead to severe human diseases [1,2]
We show that GTPBP6, a so far uncharacterized human protein, localizes to mitochondria where it plays a role in ribosome assembly, in addition to facilitating ribosome recycling
Unlike its bacterial homolog HflX, which is nonessential at normal growth conditions, GTPBP6 is required for mitochondrial gene expression and cell survival

Summary

Introduction

The biogenesis and the function of the mitochondrial ribosome is of central importance for the fitness and viability of eukaryotic cells, and mutations in genes encoding for mitochondrial ribosomal proteins or translation factors lead to severe human diseases [1,2]. How the mitochondrial ribosome assembles and which auxiliary factors are required for its function is poorly understood. It is likely that the assembly of the mitochondrial ribosome differs from that of the bacterial one and requires additional ancillary biogenesis factors. A number of assembly factors have been identified, including RNA helicases, RNA modifying enzymes, chaperones and GTPases, the list of factors required for mitochondrial ribosome biogenesis and function is far from complete [5]. GTPBP5, GTPBP7 and GTPBP10 are required for late maturation stages of the mtLSU [10,11,12,13,14,15,16]: GTPBP7 couples mtLSU assembly to intersubunit bridge formation and

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Conclusion