YbeY is required for ribosome small subunit assembly and tRNA processing in human mitochondria.

Mitochondria contain their own translation apparatus which enables them to produce the polypeptides encoded in their genome. The mitochondrially-encoded RNA components of the mitochondrial ribosome require various post-transcriptional processing steps. Additional protein factors are required to facilitate the biogenesis of the functional mitoribosome. We have characterized a mitochondrially-localized protein, YbeY, which interacts with the assembling mitoribosome through the small subunit. Loss of YbeY leads to a severe reduction in mitochondrial translation and a loss of cell viability, associated with less accurate mitochondrial tRNASer(AGY) processing from the primary transcript and a defect in the maturation of the mitoribosomal small subunit. Our results suggest that YbeY performs a dual, likely independent, function in mitochondria being involved in precursor RNA processing and mitoribosome biogenesis. Issue Section: Nucleic Acid Enzymes

Challenging Masculinity in CSR Disclosures: Silencing of Women’s Voices in Tanzania’s Mining Industry

This paper presents a feminist analysis of corporate social responsibility (CSR) in a male-dominated industry within a developing country context. It seeks to raise awareness of the silencing of women’s voices in CSR reports produced by mining companies in Tanzania. Tanzania is one of the poorest countries in Africa, and women are often marginalised in employment and social policy considerations. Drawing on work by Hélène Cixous, a post-structuralist/radical feminist scholar, the paper challenges the masculinity of CSR discourses that have repeatedly masked the voices and concerns of ‘other’ marginalised social groups, notably women. Using interpretative ethnographic case studies, the paper provides much-needed empirical evidence to show how gender imbalances remain prevalent in the Tanzanian mining sector. This evidence draws attention to the dynamics faced by many women working in or living around mining areas in Tanzania. The paper argues that CSR, a discourse enmeshed with the patriarchal logic of the contemporary capitalist system, is entangled with tensions, class conflicts and struggles which need to be unpacked and acknowledged. The paper considers the possibility of policy reforms in order to promote gender balance in the Tanzanian mining sector and create a platform for women’s concerns to be voiced

Migration von /sw vom AFS ins DCE/DFS

/sw ist eine verteilte Softwarebereitstellung mit dem Ziel, jedem Benutzer Software zentral zur Verfügung zu stellen, ohne daß er sich darum kümmern muß, woher er seine Software bekommt. Für eine Außenstehenden ergibt sich somit das Bild eines großen Softwarepools, aus dem er sich fertig installierte Software für seine Plattform herunterladen kann. Voraussetzung dafür ist, daß ein Benuzter an seiner Workstation über AFS (Andrew File System), DFS (Distributed File System) oder ftp verfügt. Zur Zeit werden vom /sw für 18 verschiedenen Unix-Plattformen 594 Programme in 1024 verschiedenen Installationen angeboten. Die meisten Architekturen vom /sw liegen im AFS, bis auf die Architekturen DEC ALPHA, IRIX 4.0 und Linux, die im NFS liegen. In Zukunft wird es für die gesamte /sw Software nur noch eine Quelle geben, das DFS. Mit der Migration von /sw aus dem AFS ins DFS entfällt dann die Trennung von /sw in einen AFS-Teil und einem NFS-Teil und damit auch der AFS/NFS-Translators, der recht unstabil läuft. Die gesamte Software von /sw wurde aus dem AFS bzw. NFS ins DFS migriert, so daß für alle vom /sw unterstützten Architekturen nur noch eine Quelle zur Verfügung steht, die Stuttgarter DCE-Zelle. Jeder AFS-Klient hat über den AFS/DFS-Translator Zugriff auf /sw und für die NFS-Klienten wird das /sw-Fi-lesystem exportiert, so daß jeder NFS-Klient die Möglichkeit hat das DFS-Filesystem /sw zu mounten. Eine Workstation kann sowohl AFS- als auch DCE/DFS-Klient sein

The catalytic activity of methyltransferase METTL15 is dispensable for its role in mitochondrial ribosome biogenesis.

Acknowledgements: We are grateful to Shujing Ding and Ian M. Fearnley for their help in the proteomic analysis and to the members of the MRC MBU Mitochondrial Genetics group for their input into this work.Publication status: PublishedFunder: Medical Research Council; FundRef: https://doi.org/10.13039/10.13039/501100000265Ribosomes are large macromolecular complexes composed of both proteins and RNA, that require a plethora of factors and post-transcriptional modifications for their biogenesis. In human mitochondria, the ribosomal RNA is post-transcriptionally modified at ten sites. The N4-methylcytidine (m4C) methyltransferase, METTL15, modifies the 12S rRNA of the small subunit at position C1486. The enzyme is essential for mitochondrial protein synthesis and assembly of the mitoribosome small subunit, as shown here and by previous studies. Here, we demonstrate that the m4C modification is not required for small subunit biogenesis, indicating that the chaperone-like activity of the METTL15 protein itself is an essential component for mitoribosome biogenesis

In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue.

Mitochondria host key metabolic processes vital for cellular energy provision and are central to cell fate decisions. They are subjected to unique genetic control by both nuclear DNA and their own multi-copy genome - mitochondrial DNA (mtDNA). Mutations in mtDNA often lead to clinically heterogeneous, maternally inherited diseases that display different organ-specific presentation at any stage of life. For a long time, genetic manipulation of mammalian mtDNA has posed a major challenge, impeding our ability to understand the basic mitochondrial biology and mechanisms underpinning mitochondrial disease. However, an important new tool for mtDNA mutagenesis has emerged recently, namely double-stranded DNA deaminase (DddA)-derived cytosine base editor (DdCBE). Here, we test this emerging tool for in vivo use, by delivering DdCBEs into mouse heart using adeno-associated virus (AAV) vectors and show that it can install desired mtDNA edits in adult and neonatal mice. This work provides proof-of-concept for use of DdCBEs to mutagenize mtDNA in vivo in post-mitotic tissues and provides crucial insights into potential translation to human somatic gene correction therapies to treat primary mitochondrial disease phenotypes

A library of base editors for the precise ablation of all protein-coding genes in the mouse mitochondrial genome.

Acknowledgements: We acknowledge the members of the Mitochondrial Genetics Group (MRC-MBU, University of Cambridge) for useful discussion during the course of this research. We thank J. Carroll for help in obtaining the data for Fig. 6f. All authors disclose funding support for the research described in this study from Medical Research Council UK (MC_UU_00015/4 and MC_UU_00028/3). P.S-P. discloses support for the research described in this study from The Champ Foundation (G112428). P.A.N. discloses support for the research described in this study from The Lily Foundation (G101554).The development of curative treatments for mitochondrial diseases, which are often caused by mutations in mitochondrial DNA (mtDNA) that impair energy metabolism and other aspects of cellular homoeostasis, is hindered by an incomplete understanding of the underlying biology and a scarcity of cellular and animal models. Here we report the design and application of a library of double-stranded-DNA deaminase-derived cytosine base editors optimized for the precise ablation of every mtDNA protein-coding gene in the mouse mitochondrial genome. We used the library, which we named MitoKO, to produce near-homoplasmic knockout cells in vitro and to generate a mouse knockout with high heteroplasmy levels and no off-target edits. MitoKO should facilitate systematic and comprehensive investigations of mtDNA-related pathways and their impact on organismal homoeostasis, and aid the generation of clinically meaningful in vivo models of mtDNA dysfunction

CSR Disclosure Practices in the Zambia Mining Industry

The main objective of this chapter is to examine the corporate social responsibility (CSR) disclosure practices and the related motivation for (or lack thereof) CSR disclosures in the Zambian mining industry. Key CSR disclosures are examined to identify the trends in disclosure. Semi-structured interviews were also conducted with the mining managers to explore the underlying motives for such disclosures (non-disclosures) and the prospects that exist for future development. We find that there is very limited CSR disclosure by mining companies in Zambia, while CSR reporting is directed mainly towards ‘public image building’ and motivated by project financing purposes for those companies with a ‘western’ parent company. We argue that the lack of demand for such reporting from the Zambian citizenry has partly contributed to the low disclosures. Some international voluntary reporting guidelines have been adopted by ‘western’ parent mining companies, while reputation risk management remains a key concern for these companies. The study contributes to understanding the underlying motives for CSR disclosures in a developing country context