Dual Function of GTPBP6 in Biogenesis and Recycling of Human Mitochondrial Ribosomes

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2020 Dec 2

PMID 33264405

Citations 28

Authors

Elena Lavdovskaia

Kart Denks

Franziska Nadler

Emely Steube

Andreas Linden

Henning Urlaub

Marina V Rodnina

Ricarda Richter-Dennerlein

Affiliations

Soon will be listed here.

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.

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References

Brown A, Amunts A, Bai X, Sugimoto Y, Edwards P, Murshudov G . Structure of the large ribosomal subunit from human mitochondria. Science. 2014; 346(6210):718-722. PMC: 4246062. DOI: 10.1126/science.1258026. View

Rorbach J, Gammage P, Minczuk M . C7orf30 is necessary for biogenesis of the large subunit of the mitochondrial ribosome. Nucleic Acids Res. 2012; 40(9):4097-109. PMC: 3351152. DOI: 10.1093/nar/gkr1282. View

Ayyub S, Gao F, Lightowlers R, Chrzanowska-Lightowlers Z . Rescuing stalled mammalian mitoribosomes - what can we learn from bacteria?. J Cell Sci. 2020; 133(1). DOI: 10.1242/jcs.231811. View

Chomyn A . In vivo labeling and analysis of human mitochondrial translation products. Methods Enzymol. 1996; 264:197-211. DOI: 10.1016/s0076-6879(96)64020-8. View

Dey S, Biswas C, Sengupta J . The universally conserved GTPase HflX is an RNA helicase that restores heat-damaged ribosomes. J Cell Biol. 2018; 217(7):2519-2529. PMC: 6028529. DOI: 10.1083/jcb.201711131. View

GRUNBERG-MANAGO M, Dessen P, Pantaloni D, Wolfe A, DONDON J . Light-scattering studies showing the effect of initiation factors on the reversible dissociation of Escherichia coli ribosomes. J Mol Biol. 1975; 94(3):461-78. DOI: 10.1016/0022-2836(75)90215-6. View

Schneider H, Berthold J, Bauer M, Dietmeier K, Guiard B, Brunner M . Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature. 1994; 371(6500):768-74. DOI: 10.1038/371768a0. View

Zhang Y, Mandava C, Cao W, Li X, Zhang D, Li N . HflX is a ribosome-splitting factor rescuing stalled ribosomes under stress conditions. Nat Struct Mol Biol. 2015; 22(11):906-13. DOI: 10.1038/nsmb.3103. View

Greber B, Ban N . Structure and Function of the Mitochondrial Ribosome. Annu Rev Biochem. 2016; 85:103-32. DOI: 10.1146/annurev-biochem-060815-014343. View

10.

Gagnon M, Seetharaman S, Bulkley D, Steitz T . Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome. Science. 2012; 335(6074):1370-2. PMC: 3377438. DOI: 10.1126/science.1217443. View

11.

De Silva D, Tu Y, Amunts A, Fontanesi F, Barrientos A . Mitochondrial ribosome assembly in health and disease. Cell Cycle. 2015; 14(14):2226-50. PMC: 4615001. DOI: 10.1080/15384101.2015.1053672. View

12.

He J, Cooper H, Reyes A, Di Re M, Kazak L, Wood S . Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit. Nucleic Acids Res. 2012; 40(13):6097-108. PMC: 3401442. DOI: 10.1093/nar/gks257. View

13.

Richter R, Rorbach J, Pajak A, Smith P, Wessels H, Huynen M . A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. EMBO J. 2010; 29(6):1116-25. PMC: 2845271. DOI: 10.1038/emboj.2010.14. View

14.

Stetefeld J, McKenna S, Patel T . Dynamic light scattering: a practical guide and applications in biomedical sciences. Biophys Rev. 2017; 8(4):409-427. PMC: 5425802. DOI: 10.1007/s12551-016-0218-6. View

15.

Pearce S, Rebelo-Guiomar P, DSouza A, Powell C, Van Haute L, Minczuk M . Regulation of Mammalian Mitochondrial Gene Expression: Recent Advances. Trends Biochem Sci. 2017; 42(8):625-639. PMC: 5538620. DOI: 10.1016/j.tibs.2017.02.003. View

16.

Wanschers B, Szklarczyk R, Pajak A, van den Brand M, Gloerich J, Rodenburg R . C7orf30 specifically associates with the large subunit of the mitochondrial ribosome and is involved in translation. Nucleic Acids Res. 2012; 40(9):4040-51. PMC: 3351149. DOI: 10.1093/nar/gkr1271. View

17.

Jain N, Vithani N, Rafay A, Prakash B . Identification and characterization of a hitherto unknown nucleotide-binding domain and an intricate interdomain regulation in HflX-a ribosome binding GTPase. Nucleic Acids Res. 2013; 41(20):9557-69. PMC: 3814362. DOI: 10.1093/nar/gkt705. View

18.

Rodnina M, Wintermeyer W . GTP consumption of elongation factor Tu during translation of heteropolymeric mRNAs. Proc Natl Acad Sci U S A. 1995; 92(6):1945-9. PMC: 42399. DOI: 10.1073/pnas.92.6.1945. View

19.

Duval M, Dar D, Carvalho F, Rocha E, Sorek R, Cossart P . HflXr, a homolog of a ribosome-splitting factor, mediates antibiotic resistance. Proc Natl Acad Sci U S A. 2018; 115(52):13359-13364. PMC: 6310831. DOI: 10.1073/pnas.1810555115. View

20.

Uchiumi T, Ohgaki K, Yagi M, Aoki Y, Sakai A, Matsumoto S . ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation. Nucleic Acids Res. 2010; 38(16):5554-68. PMC: 2938226. DOI: 10.1093/nar/gkq305. View