bims-mitran 2022-10-23 papers

Issue of 2022‒10‒23
three papers selected by
Andreas Kohler

Nat Commun. 2022 Oct 17. 13(1): 6132

Structure of a mitochondrial ribosome with fragmented rRNA in complex with membrane-targeting elements.

Victor Tobiasson, Ieva Berzina, Alexey Amunts.

Mitoribosomes of green algae display a great structural divergence from their tracheophyte relatives, with fragmentation of both rRNA and proteins as a defining feature. Here, we report a 2.9 Å resolution structure of the mitoribosome from the alga Polytomella magna harbouring a reduced rRNA split into 13 fragments. We found that the rRNA contains a non-canonical reduced form of the 5S, as well as a permutation of the LSU domain I. The mt-5S rRNA is stabilised by mL40 that is also found in mitoribosomes lacking the 5S, which suggests an evolutionary pathway. Through comparison to other ribosomes with fragmented rRNAs, we observe that the pattern is shared across large evolutionary distances, and between cellular compartments, indicating an evolutionary convergence and supporting the concept of a primordial fragmented ribosome. On the protein level, eleven peripherally associated HEAT-repeat proteins are involved in the binding of 3' rRNA termini, and the structure features a prominent pseudo-trimer of one of them (mL116). Finally, in the exit tunnel, mL128 constricts the tunnel width of the vestibular area, and mL105, a homolog of a membrane targeting component mediates contacts with an inner membrane bound insertase. Together, the structural analysis provides insight into the evolution of the ribosomal machinery in mitochondria.

DOI: https://doi.org/10.1038/s41467-022-33582-5

Biochim Biophys Acta Gen Subj. 2022 Oct 17. pii: S0304-4165(22)00173-8. [Epub ahead of print] 130255

Silencing of the mitochondrial ribosomal protein L-24 gene activates the oxidative stress response in Caenorhabditis elegans.

Graziella Ficociello, Emily Schifano, Michela Di Nottia, Alessandra Torraco, Rosalba Carrozzo, Daniela Uccelletti, Arianna Montanari.

The mitochondrial translation machinery allows the synthesis of the mitochondrial-encoded subunits of the electron transport chain. Defects in this process lead to mitochondrial physiology failure; in humans, they are associated with early-onset, extremely variable and often fatal disorder. The use of a simple model to study the mitoribosomal defects is mandatory to overcome the difficulty to analyze the impact of pathological mutations in humans. In this paper we study in nematode Caenorhabditis elegans the silencing effect of the mrpl-24 gene, coding for the mitochondrial ribosomal protein L-24 (MRPL-24). This is a structural protein of the large subunit 39S of the mitoribosome and its effective physiological function is not completely elucidated. We have evaluated the nematode's fitness fault and investigated the mitochondrial defects associated with MRPL-24 depletion. The oxidative stress response activation due to the mitochondrial alteration has been also investigated as a compensatory physiological mechanism. For the first time, we demonstrated that MRPL-24 reduction increases the expression of detoxifying enzymes such as SOD-3 and GST-4 through the involvement of transcription factor SKN-1.BACKGROUND: In humans, mutations in genes encoding mitochondrial ribosomal proteins (MRPs) often cause early-onset, severe, fatal and extremely variable clinical defects. Mitochondrial ribosomal protein L-24 (MRPL24) is a structural protein of the large subunit 39S of the mitoribosome. It is highly conserved in different species and its effective physiological function is not completely elucidated.
METHODS: We characterized the MRPL24 functionality using the animal model Caenorhabditis elegans. We performed the RNA mediated interference (RNAi) by exposing the nematodes' embryos to double-stranded RNA (dsRNA) specific for the MRPL-24 coding sequence. We investigated for the first time in C. elegans, the involvement of the MRPL-24 on the nematode's fitness and its mitochondrial physiology.
RESULTS: Mrpl-24 silencing in C. elegans negatively affected the larval development, progeny production and body bending. The analysis of mitochondrial functionality revealed loss of mitochondrial network and impairment of mitochondrial functionality, as the decrease of oxygen consumption rate and the ROS production, as well as reduction of mitochondrial protein synthesis. Finally, the MRPL-24 depletion activated the oxidative stress response, increasing the expression levels of two detoxifying enzymes, SOD-3 and GST-4.
CONCLUSIONS: In C. elegans the MRPL-24 depletion activated the oxidative stress response. This appears as a compensatory mechanism to the alteration of the mitochondrial functionality and requires the involvement of transcription factor SKN-1.
GENERAL SIGNIFICANCE: C. elegans resulted in a good model for the study of mitochondrial disorders and its use as a simple and pluricellular organism could open interesting perspectives to better investigate the pathologic mechanisms underlying these devastating diseases.

Keywords: Caenorhabditis elegans; MRPL-24 mitoribosomal protein; Mitochondrial translation; Oxidative stress response; SKN-1 transcription factor

DOI: https://doi.org/10.1016/j.bbagen.2022.130255

Wiley Interdiscip Rev RNA. 2022 Oct 18. e1766

Caught in the act-Visualizing ribonucleases during eukaryotic ribosome assembly.

Claudia Schneider, Katherine E Bohnsack.

Ribosomes are essential macromolecular machines responsible for translating the genetic information encoded in mRNAs into proteins. Ribosomes are composed of ribosomal RNAs and proteins (rRNAs and RPs) and the rRNAs fulfill both catalytic and architectural functions. Excision of the mature eukaryotic rRNAs from their precursor transcript is achieved through a complex series of endoribonucleolytic cleavages and exoribonucleolytic processing steps that are precisely coordinated with other aspects of ribosome assembly. Many ribonucleases involved in pre-rRNA processing have been identified and pre-rRNA processing pathways are relatively well defined. However, momentous advances in cryo-electron microscopy have recently enabled structural snapshots of various pre-ribosomal particles from budding yeast (Saccharomyces cerevisiae) and human cells to be captured and, excitingly, these structures not only allow pre-rRNAs to be observed before and after cleavage events, but also enable ribonucleases to be visualized on their target RNAs. These structural views of pre-rRNA processing in action allow a new layer of understanding of rRNA maturation and how it is coordinated with other aspects of ribosome assembly. They illuminate mechanisms of target recognition by the diverse ribonucleases involved and reveal how the cleavage/processing activities of these enzymes are regulated. In this review, we discuss the new insights into pre-rRNA processing gained by structural analyses and the growing understanding of the mechanisms of ribonuclease regulation. This article is categorized under: Translation > Ribosome Biogenesis RNA Processing > rRNA Processing.

Keywords: RNA exosome; RNA processing; ribonuclease; ribosome biogenesis

DOI: https://doi.org/10.1002/wrna.1766