bims-tricox 2023-11-05 papers

Issue of 2023–11–05
four papers selected by
Yash Verma, University of Zurich

BMC Plant Biol. 2023 Nov 03. 23(1): 538

The nucleolar protein NOL12 is required for processing of large ribosomal subunit rRNA precursors in Arabidopsis.

Monika Zakrzewska-Placzek, Anna Golisz-Mocydlarz, Michal Krzyszton, Justyna Piotrowska, Malgorzata Lichocka, Joanna Kufel.

BACKGROUND: NOL12 5'-3' exoribonucleases, conserved among eukaryotes, play important roles in pre-rRNA processing, ribosome assembly and export. The most well-described yeast counterpart, Rrp17, is required for maturation of 5.8 and 25S rRNAs, whereas human hNOL12 is crucial for the separation of the large (LSU) and small (SSU) ribosome subunit rRNA precursors.
RESULTS: In this study we demonstrate that plant AtNOL12 is also involved in rRNA biogenesis, specifically in the processing of the LSU rRNA precursor, 27S pre-rRNA. Importantly, the absence of AtNOL12 alters the expression of many ribosomal protein and ribosome biogenesis genes. These changes could potentially exacerbate rRNA biogenesis defects, or, conversely, they might stem from the disturbed ribosome assembly caused by delayed pre-rRNA processing. Moreover, exposure of the nol12 mutant to stress factors, including heat and pathogen Pseudomonas syringae, enhances the observed molecular phenotypes, linking pre-rRNA processing to stress response pathways. The aberrant rRNA processing, dependent on AtNOL12, could impact ribosome function, as suggested by improved mutant resistance to ribosome-targeting antibiotics.
CONCLUSION: Despite extensive studies, the pre-rRNA processing pathway in plants remains insufficiently characterized. Our investigation reveals the involvement of AtNOL12 in the maturation of rRNA precursors, correlating this process to stress response in Arabidopsis. These findings contribute to a more comprehensive understanding of plant ribosome biogenesis.

Keywords: Arabidopsis thaliana; Nucleolus; Ribosome biogenesis; Stress response; pre-rRNA processing; rRNA

DOI: https://doi.org/10.1186/s12870-023-04561-9

Nat Commun. 2023 Oct 31. 14(1): 6961

The structure of a hibernating ribosome in a Lyme disease pathogen.

Manjuli R Sharma, Swati R Manjari, Ekansh K Agrawal, Pooja Keshavan, Ravi K Koripella, Soneya Majumdar, Ashley L Marcinkiewicz, Yi-Pin Lin, Rajendra K Agrawal, Nilesh K Banavali.

The spirochete bacterial pathogen Borrelia (Borreliella) burgdorferi (Bbu) affects more than 10% of the world population and causes Lyme disease in about half a million people in the US annually. Therapy for Lyme disease includes antibiotics that target the Bbu ribosome. Here we present the structure of the Bbu 70S ribosome obtained by single particle cryo-electron microscopy at 2.9 Å resolution, revealing a bound hibernation promotion factor protein and two genetically non-annotated ribosomal proteins bS22 and bL38. The ribosomal protein uL30 in Bbu has an N-terminal α-helical extension, partly resembling the mycobacterial bL37 protein, suggesting evolution of bL37 and a shorter uL30 from a longer uL30 protein. Its analogy to proteins uL30m and mL63 in mammalian mitochondrial ribosomes also suggests a plausible evolutionary pathway for expansion of protein content in mammalian mitochondrial ribosomes. Computational binding free energy predictions for antibiotics reflect subtle distinctions in antibiotic-binding sites in the Bbu ribosome. Discovery of these features in the Bbu ribosome may enable better ribosome-targeted antibiotic design for Lyme disease treatment.

DOI: https://doi.org/10.1038/s41467-023-42266-7

Trends Cell Biol. 2023 Oct 30. pii: S0962-8924(23)00208-8. [Epub ahead of print]

Mitochondrial complexome and import network.

Fabian den Brave, Uwe Schulte, Bernd Fakler, Nikolaus Pfanner, Thomas Becker.

Mitochondria perform crucial functions in cellular metabolism, protein and lipid biogenesis, quality control, and signaling. The systematic analysis of protein complexes and interaction networks provided exciting insights into the structural and functional organization of mitochondria. Most mitochondrial proteins do not act as independent units, but are interconnected by stable or dynamic protein-protein interactions. Protein translocases are responsible for importing precursor proteins into mitochondria and form central elements of several protein interaction networks. These networks include molecular chaperones and quality control factors, metabolite channels and respiratory chain complexes, and membrane and organellar contact sites. Protein translocases link the distinct networks into an overarching network, the mitochondrial import network (MitimNet), to coordinate biogenesis, membrane organization and function of mitochondria.

Keywords: cell organelles; energetics; metabolism; mitochondria; morphology; protein assembly; protein networks; protein sorting

DOI: https://doi.org/10.1016/j.tcb.2023.10.004

Cell Rep. 2023 Nov 01. pii: S2211-1247(23)01371-2. [Epub ahead of print]42(11): 113359

The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress.

Sezen Meydan, Géssica C Barros, Vanessa Simões, Lana Harley, Blanche K Cizubu, Nicholas R Guydosh, Gustavo M Silva.

Oxidative stress causes K63-linked ubiquitination of ribosomes by the E2 ubiquitin conjugase Rad6. How Rad6-mediated ubiquitination of ribosomes affects translation, however, is unclear. We therefore perform Ribo-seq and Disome-seq in Saccharomyces cerevisiae and show that oxidative stress causes ribosome pausing at specific amino acid motifs, which also leads to ribosome collisions. However, these redox-pausing signatures are lost in the absence of Rad6 and do not depend on the ribosome-associated quality control (RQC) pathway. We also show that Rad6 is needed to inhibit overall translation in response to oxidative stress and that its deletion leads to increased expression of antioxidant genes. Finally, we observe that the lack of Rad6 leads to changes during translation that affect activation of the integrated stress response (ISR) pathway. Our results provide a high-resolution picture of the gene expression changes during oxidative stress and unravel an additional stress response pathway affecting translation elongation.

Keywords: CP: Molecular biology; Rad6; oxidative stress; ribosome pause; ribosome ubiquitination; stress response; translation control

DOI: https://doi.org/10.1016/j.celrep.2023.113359