Ribosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209004 | PMC |
| http://dx.doi.org/10.1038/s41467-021-23702-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A truncated variant of the ribosome-associated trigger factor specifically contributes to plant chloroplast ribosome biogenesis.
Nat Commun
January 2025
Molecular Genetics of Eukaryotes, University of Kaiserslautern, Kaiserslautern, Germany.
Molecular chaperones are essential throughout a protein's life and act already during protein synthesis. Bacteria and chloroplasts of plant cells share the ribosome-associated chaperone trigger factor (Tig1 in plastids), facilitating maturation of emerging nascent polypeptides. While typical trigger factor chaperones employ three domains for their task, the here described truncated form, Tig2, contains just the ribosome binding domain.
View Article and Find Full Text PDFHN1 Functions in Protein Synthesis Regulation via mTOR-RPS6 Axis and Maintains Nucleolar Integrity.
Cell Prolif
January 2025
Faculty of Engineering, Department of Bioengineering, Cancer Biology Laboratory, Ege University, Bornova, Izmir, Turkey.
Haematological and Neurological Expressed 1 (HN1) is an oncogene for various cancers and previously has been linked with centrosome clustering and cell cycle pathways. Moreover, HN1 has recently been reported to activate mTOR signalling, which is the regulator of ribosome biogenesis and maintenance. We explored the role of HN1 in mTOR signalling through various gain- and loss-of-function experiments using biochemical approaches in different cell lines.
View Article and Find Full Text PDFThe heart employs a specialized ribosome in its muscle cells to translate genetic information into proteins, a fundamental adaptation with an elusive physiological role. Its significance is underscored by the discovery of neonatal patients suffering from often fatal heart failure caused by rare compound heterozygous variants in RPL3L, a muscle-specific ribosomal protein that replaces the ubiquitous RPL3 in cardiac ribosomes. -linked heart failure represents the only known human disease arising from mutations in tissue-specific ribosomes, yet the underlying pathogenetic mechanisms remain poorly understood despite an increasing number of reported cases.
View Article and Find Full Text PDFThe role of immune cells in neurodegeneration remains incompletely understood. Our recent study revealed the presence of mucosal-associated invariant T (MAIT) cells in the meninges, where they express antioxidant molecules to maintain meningeal barrier integrity. Accumulation of misfolded tau proteins are a hallmark of neurodegenerative diseases.
View Article and Find Full Text PDFFunction analysis of RNase III in response to oxidative stress in Synechocystis sp. PCC 6803.
Microbiol Res
January 2025
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address:
RNase III, a ubiquitously distributed endonuclease, plays an important role in RNA processing and functions as a global regulator of gene expression. In this study, we explored the role of RNase III in mediating the oxidative stress response in Synechocystis sp. PCC 6803.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!