bims-tricox Biomed News
on Translation, ribosomes and COX
Issue of 2022‒09‒18
six papers selected by
Yash Verma
University of Delhi South Campus
  1. Schizosaccharomyces pombe Sls1 is primarily required for cox1 mRNA translation.
  2. Making the leap from structure to mechanism: are the open states of mammalian complex I identified by cryoEM resting states or catalytic intermediates?
  3. Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover.
  4. The daunting task of modifying ribosomal RNA.
  5. Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1.
  6. RNA structure mediated thermoregulation: What can we learn from plants?
  1. Yeast. 2022 Sep 11.
    Schizosaccharomyces pombe Sls1 is primarily required for cox1 mRNA translation.
    Yirong Wang, Ying Luo, Ying Huang.
      Mitochondrial DNA (mtDNA) encodes essential subunits of the oxidative phosphorylation (OXPHOS) complexes, thus the expression of mtDNA-encoded genes is essential for the synthesis of adenosine triphosphate (ATP). However, factors involved in mitochondrial translation have not been fully characterized. In this study, we characterized Schizosaccharomyces pombe Sls1, which has sequence similarity to Saccharomyces cerevisiae Sls1 that is required for the translation of all mtDNA-encoded mRNAs. Deletion of S. pombe sls1 severely impaired the growth of the cells on a rich medium containing the non-fermentable carbon source glycerol, which requires mitochondrial respiration. We found that the translation of mtDNA-encoded Cox1, the largest subunit of the cytochrome c oxidase complex, was severely impaired in Δsls1 cells. Deletion of S. pombe sls1 also resulted in a barely detectable steady-state level of mature cox1 mRNA. RNA immunoprecipitation showed that S. pombe Sls1 interacts with cox1 mRNA. Sucrose gradient sedimentation analysis revealed that S. pombe Sls1 is associated with the small subunit of mitochondrial ribosomes. Our results suggest that unlike S. cerevisiae Sls1, S. pombe Sls1 is primarily required for the accumulation and translation of cox1 mRNA. This article is protected by copyright. All rights reserved.
    Keywords:  Cox1; Mitochondria; Schizosaccharomyces pombe; Translation
    DOI:  https://doi.org/10.1002/yea.3813
  2. Curr Opin Struct Biol. 2022 Sep 07. pii: S0959-440X(22)00126-9. [Epub ahead of print]77 102447
    Making the leap from structure to mechanism: are the open states of mammalian complex I identified by cryoEM resting states or catalytic intermediates?
    Injae Chung, Daniel N Grba, John J Wright, Judy Hirst.
      Respiratory complex I (NADH:ubiquinone oxidoreductase) is a multi-subunit, energy-transducing mitochondrial enzyme that is essential for oxidative phosphorylation and regulating NAD+/NADH pools. Despite recent advances in structural knowledge and a long history of biochemical analyses, the mechanism of redox-coupled proton translocation by complex I remains unknown. Due to its ability to separate molecules in a mixed population into distinct classes, single-particle electron cryomicroscopy has enabled identification and characterisation of different complex I conformations. However, deciding on their catalytic and/or regulatory properties to underpin mechanistic hypotheses, especially without detailed biochemical characterisation of the structural samples, has proven challenging. In this review we explore different mechanistic interpretations of the closed and open states identified in cryoEM analyses of mammalian complex I.
    DOI:  https://doi.org/10.1016/j.sbi.2022.102447
  3. Mol Cell. 2022 Sep 15. pii: S1097-2765(22)00807-3. [Epub ahead of print]82(18): 3424-3437.e8
    Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover.
    Sihan Li, Ken Ikeuchi, Misaki Kato, Robert Buschauer, Takato Sugiyama, Shungo Adachi, Hideo Kusano, Tohru Natsume, Otto Berninghausen, Yoshitaka Matsuo, Thomas Becker, Roland Beckmann, Toshifumi Inada.
      Cells can respond to stalled ribosomes by sensing ribosome collisions and employing quality control pathways. How ribosome stalling is resolved without collisions, however, has remained elusive. Here, focusing on noncolliding stalling exhibited by decoding-defective ribosomes, we identified Fap1 as a stalling sensor triggering 18S nonfunctional rRNA decay via polyubiquitination of uS3. Ribosome profiling revealed an enrichment of Fap1 at the translation initiation site but also an association with elongating individual ribosomes. Cryo-EM structures of Fap1-bound ribosomes elucidated Fap1 probing the mRNA simultaneously at both the entry and exit channels suggesting an mRNA stasis sensing activity, and Fap1 sterically hinders the formation of canonical collided di-ribosomes. Our findings indicate that individual stalled ribosomes are the potential signal for ribosome dysfunction, leading to accelerated turnover of the ribosome itself.
    Keywords:  E3 ubiquitin ligase; cryo-EM; individual ribosomes; mRNA stasis sensing; rRNA decay; ribosomal stalling; ribosome profiling; translational quality control; ubiquitination
    DOI:  https://doi.org/10.1016/j.molcel.2022.08.018
  4. RNA. 2022 Sep 15. pii: rna.079391.122. [Epub ahead of print]
    The daunting task of modifying ribosomal RNA.
    U Thomas Meier.
      One of the most basic tasks of every cell is the synthesis of ribosomes, yet the process is so complex that we are only beginning to comprehend it. In human cells, the final product contains four RNAs and 79 proteins forming a large ribonucleoprotein, the ribosome. About twice as many factors are involved in assembly of these protein synthesizing machines. Additionally, some 200 small nucleolar ribonucleoproteins (snoRNPs) function in the modification of pre-ribosomal RNA (pre-rRNA) at a similar number of ribonucleotides. Modification is essential for proper function and biogenesis of ribosomes (Decatur and Fournier 2002; Sloan et al. 2016). While abrogation of individual modifications has little to no measurable effects, removal of a combination of modifications or of all causes severe to lethal effects. Modifications mostly cluster around the functional centers of the ribosome and some modifications are important for ribosome assembly. The subject of this perspective is to raise awareness to how modification at so many sites can be achieved while the pre-rRNA is being processed, folded and re-folded, and assembled with ribosomal proteins to yield the pre-ribosomal subunits in the nucleolus (Baßler and Hurt 2019). This is not a comprehensive review but a simplification of complex issues providing access to the general reader.
    Keywords:  RNA modification; ribosomal RNA; snoRNAs; snoRNPs
    DOI:  https://doi.org/10.1261/rna.079391.122
  5. Nat Struct Mol Biol. 2022 Sep 12.
    Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1.
    Michael Prattes, Irina Grishkovskaya, Victor-Valentin Hodirnau, Christina Hetzmannseder, Gertrude Zisser, Carolin Sailer, Vasileios Kargas, Mathias Loibl, Magdalena Gerhalter, Lisa Kofler, Alan J Warren, Florian Stengel, David Haselbach, Helmut Bergler.
      The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large ribosomal subunit. Drg1 releases the shuttling maturation factor Rlp24 from pre-60S particles shortly after nuclear export, a strict requirement for downstream maturation. The molecular mechanism of release remained elusive. Here, we report a series of cryo-EM structures that captured the extraction of Rlp24 from pre-60S particles by Saccharomyces cerevisiae Drg1. These structures reveal that Arx1 and the eukaryote-specific rRNA expansion segment ES27 form a joint docking platform that positions Drg1 for efficient extraction of Rlp24 from the pre-ribosome. The tips of the Drg1 N domains thereby guide the Rlp24 C terminus into the central pore of the Drg1 hexamer, enabling extraction by a hand-over-hand translocation mechanism. Our results uncover substrate recognition and processing by Drg1 step by step and provide a comprehensive mechanistic picture of the conserved modus operandi of AAA-ATPases.
    DOI:  https://doi.org/10.1038/s41594-022-00832-5
  6. Front Plant Sci. 2022 ;13 938570
    RNA structure mediated thermoregulation: What can we learn from plants?
    Sherine E Thomas, Martin Balcerowicz, Betty Y-W Chung.
      RNA molecules have the capacity to form a multitude of distinct secondary and tertiary structures, but only the most energetically favorable conformations are adopted at any given time. Formation of such structures strongly depends on the environment and consequently, these structures are highly dynamic and may refold as their surroundings change. Temperature is one of the most direct physical parameters that influence RNA structure dynamics, and in turn, thermosensitive RNA structures can be harnessed by a cell to perceive and respond to its temperature environment. Indeed, many thermosensitive RNA structures with biological function have been identified in prokaryotic organisms, but for a long time such structures remained elusive in eukaryotes. Recent discoveries, however, reveal that thermosensitive RNA structures are also found in plants, where they affect RNA stability, pre-mRNA splicing and translation efficiency in a temperature-dependent manner. In this minireview, we provide a short overview of thermosensitive RNA structures in prokaryotes and eukaryotes, highlight recent advances made in identifying such structures in plants and discuss their similarities and differences to established prokaryotic RNA thermosensors.
    Keywords:  RNA structure; plants; protein synthesis; temperature; thermosensor; translation
    DOI:  https://doi.org/10.3389/fpls.2022.938570
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