bims-tricox Biomed News
on Translation, ribosomes and COX
Issue of 2022–09–04
eight papers selected by
Yash Verma, University of Delhi South Campus
  1. Biallelic pathogenic variants in COX11 are associated with an infantile-onset mitochondrial encephalopathy.
  2. The prokaryotic activity of the IGR IRESs is mediated by ribosomal protein S1.
  3. End-to-end pipeline for differential analysis of pausing in ribosome profiling data.
  4. Selective recruitment of stress-responsive mRNAs to ribosomes for translation by acetylated protein S1 during nutrient stress in Escherichia coli.
  5. FRIENDLY (FMT) is an RNA binding protein associated with cytosolic ribosomes at the mitochondrial surface.
  6. Unveiling the functions of plastid ribosomal proteins in plant development and abiotic stress tolerance.
  7. Translating while under attack: Plant defense mRNAs find a way.
  8. NMR resonance assignment of the N-terminal GTPase domain of human Miro2 Bound to GTP.
  1. Hum Mutat. 2022 Aug 28.
    Biallelic pathogenic variants in COX11 are associated with an infantile-onset mitochondrial encephalopathy.
    Rocio Rius, Neal K Bennett, Kaustuv Bhattacharya, Lisa G Riley, Zafer Yüksel, Luke E Formosa, Alison G Compton, Russell C Dale, Mark J Cowley, Velimir Gayevskiy, Saeed Al Tala, Abdulrahman A Almehery, Michael T Ryan, David R Thorburn, Ken Nakamura, John Christodoulou.
      Primary mitochondrial diseases are a group of genetically and clinically heterogeneous disorders resulting from oxidative phosphorylation (OXPHOS) defects. COX11 encodes a copper chaperone that participates in the assembly of complex IV (CIV) and has not been previously linked to human disease. In a previous study, we identified that COX11 knockdown decreased cellular ATP derived from respiration, and that ATP levels could be restored with CoQ10 supplementation. This finding is surprising since COX11 has no known role in CoQ10 biosynthesis. Here, we report a novel gene-disease association by identifying biallelic pathogenic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated families using trio genome and exome sequencing. Functional studies showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ10 . These results not only suggest that COX11 variants cause defects in energy production but reveal a potential metabolic therapeutic strategy for patients with COX11 variants. This article is protected by copyright. All rights reserved.
    Keywords:  COX11; Coenzyme Q; OXPHOS; mitochondrial disorders
    DOI:  https://doi.org/10.1002/humu.24453
  2. Nucleic Acids Res. 2022 Aug 30. pii: gkac697. [Epub ahead of print]
    The prokaryotic activity of the IGR IRESs is mediated by ribosomal protein S1.
    Luc Roberts, Hans-Joachim Wieden.
      Internal ribosome entry sites (IRESs) are RNA elements capable of initiating translation on an internal portion of a messenger RNA. The intergenic region (IGR) IRES of the Dicistroviridae virus family folds into a triple pseudoknot tertiary structure, allowing it to recruit the ribosome and initiate translation in a structure dependent manner. This IRES has also been reported to drive translation in Escherichia coli and to date is the only described translation initiation signal that functions across domains of life. Here we show that unlike in the eukaryotic context the tertiary structure of the IGR IRES is not required for prokaryotic ribosome recruitment. In E. coli IGR IRES translation efficiency is dependent on ribosomal protein S1 in conjunction with an AG-rich Shine-Dalgarno-like element, supporting a model where the translational activity of the IGR IRESs is due to S1-mediated canonical prokaryotic translation.
    DOI:  https://doi.org/10.1093/nar/gkac697
  3. STAR Protoc. 2022 Sep 16. 3(3): 101605
    End-to-end pipeline for differential analysis of pausing in ribosome profiling data.
    Keegan Flanagan, Wanxin Li, Ethan J Greenblatt, Khanh Dao Duc.
      Ribosome profiling is a powerful technique which maps the distribution of ribosomes along mRNAs to analyze translation genome-wide. Ribosome density can be affected by multiple factors, such as changes to translation initiation or elongation rates. We describe the application of a metric for identifying genes rate-limited by these rates by analyzing the relative distribution of ribosome footprints along transcripts. This protocol also details two sample analyses comparing gene translation efficiencies and the distribution of ribosome densities on downloadable datasets. For complete details on the use and execution of this protocol, please refer to Flanagan et al. (2022).
    Keywords:  Bioinformatics; Genomics; Sequence analysis
    DOI:  https://doi.org/10.1016/j.xpro.2022.101605
  4. Commun Biol. 2022 Sep 01. 5(1): 892
    Selective recruitment of stress-responsive mRNAs to ribosomes for translation by acetylated protein S1 during nutrient stress in Escherichia coli.
    Bai-Qing Zhang, Zong-Qin Chen, Yu-Qi Dong, Di You, Ying Zhou, Bang-Ce Ye.
      The chemical modification of ribosomes plays an important regulatory role in cellular translation adaptation in response to environmental stresses. Nevertheless, how the modified ribosome reprograms the translation machinery for the preferential expression of the specific mRNAs encoding stress-responsive proteins to stress remains poorly understood. Here, we find that AcP-induced acetylation of K411 and K464 in ribosomal protein S1 during carbon-nitrogen imbalance, which in turn impacts its binding with distinct mRNAs. S1 acetylation shows differential selectivity for recruiting subsets of mRNAs to ribosomes. Using the RNC-Seq method, we find that mimic acetylated S1 prefers transcripts related with the formation of flagella/biofilms, two-component systems, nitrogen assimilation, amino acid degradation, and lipopolysaccharide biosynthesis, whereas inhibits the translation of mRNAs involved in amino acid biosynthesis and most ribosomal proteins. Importantly, further characterization of S1-binding site (SBS) sequences of mRNAs with different translation efficiencies indicated that the presence of a conserved motif allows coordinated regulation of S1 acetylation-driven translation reprogramming for cell survival during nitrogen starvation. These findings expand the repertoire of ribosome heterogeneity to the acetylation level of S1 at specific sites and its role in the ribosome-mediated regulation of gene expression as a cellular response at the translational level to stress.
    DOI:  https://doi.org/10.1038/s42003-022-03853-4
  5. Plant J. 2022 Sep 01.
    FRIENDLY (FMT) is an RNA binding protein associated with cytosolic ribosomes at the mitochondrial surface.
    Mickaele Hemono, Thalia Salinas-Giegé, Jeanne Roignant, Audrey Vingadassalon, Philippe Hammann, Elodie Ubrig, Patryk Ngondo, Anne-Marie Duchêne.
      The spatial organization of protein synthesis in the eukaryotic cell is essential for maintaining the integrity of the proteome and the functioning of the cell. Translation on free polysomes or on ribosomes associated with the endoplasmic reticulum has been studied for a long time. More recent data have revealed selective translation of mRNAs in other compartments, in particular at the surface of mitochondria. Although these processes have been described in many organisms, in particular in plants, the mRNA targeting and localized translation mechanisms remain poorly understood. Here, the Arabidopsis thaliana Friendly (FMT) protein is shown to be a cytosolic RNA binding protein that associates with cytosolic ribosomes at the surface of mitochondria. As previously shown (El Zawily et al., 2014), FMT knock-out delays seedling development and causes mitochondrial clustering. The mutation also disrupts the mitochondrial proteome, and the localization of nuclear transcripts encoding mitochondrial proteins at the surface of mitochondria. These data indicate that FMT participates in the localization of mRNAs and their translation at the surface of mitochondria.
    Keywords:  co-translational import; localized translation; mRNA trafficking
    DOI:  https://doi.org/10.1111/tpj.15962
  6. Plant Physiol Biochem. 2022 Aug 02. pii: S0981-9428(22)00343-6. [Epub ahead of print]189 35-45
    Unveiling the functions of plastid ribosomal proteins in plant development and abiotic stress tolerance.
    Pedro Robles, Víctor Quesada.
      Translation of mRNAs into proteins is a universal process and ribosomes are the molecular machinery that carries it out. In eukaryotic cells, ribosomes can be found in the cytoplasm, mitochondria, and also in the chloroplasts of photosynthetic organisms. A number of genetic studies have been performed to determine the function of plastid ribosomal proteins (PRPs). Tobacco has been frequently used as a system to study the ribosomal proteins encoded by the chloroplast genome. In contrast, Arabidopsis thaliana and rice are preferentially used models to study the function of nuclear-encoded PRPs by using direct or reverse genetics approaches. The results of these works have provided a relatively comprehensive catalogue of the roles of PRPs in different plant biology aspects, which highlight that some PRPs are essential, while others are not. The latter ones are involved in chloroplast biogenesis, lateral root formation, leaf morphogenesis, plant growth, photosynthesis or chlorophyll synthesis. Furthermore, small gene families encode some PRPs. In the last few years, an increasing number of findings have revealed a close association between PRPs and tolerance to adverse environmental conditions. Sometimes, the same PRP can be involved in both developmental processes and the response to abiotic stress. The aim of this review is to compile and update the findings hitherto published on the functional analysis of PRPs. The study of the phenotypic effects caused by the disruption of PRPs from different species reveals the involvement of PRPs in different biological processes and highlights the significant impact of plastid translation on plant biology.
    Keywords:  Abiotic stress; Arabidopsis; Chlororibosome; Development; Mutant; Plastid ribosomal proteins (PRPs); Plastid translation
    DOI:  https://doi.org/10.1016/j.plaphy.2022.07.029
  7. Mol Cell. 2022 Sep 01. pii: S1097-2765(22)00762-6. [Epub ahead of print]82(17): 3124-3125
    Translating while under attack: Plant defense mRNAs find a way.
    Kyusik Q Kim, Hani S Zaher.
      In plants, pattern-triggered immunity shuts down global translation while allowing the translation of defense mRNAs. Wang et al. (2022) describe a previously unknown mechanism for how elements in the 5' UTR of these mRNAs can recruit the translation machinery to initiate protein synthesis.
    DOI:  https://doi.org/10.1016/j.molcel.2022.08.009
  8. Biomol NMR Assign. 2022 Sep 01.
    NMR resonance assignment of the N-terminal GTPase domain of human Miro2 Bound to GTP.
    Cassandra E Smith, David N M Jones.
      Miro2 and Miro1 are mitochondrial-associated proteins critical for regulating mitochondrial movement within the cell. Both Miro1 and Miro2 have roles in promoting neuron function, but recently Miro2 has been shown to have additional roles in response to nutrient starvation in tumor cells. Miro1 and 2 consist of two small GTPase domains flanking a pair of EF-hands. The N-terminal GTPase (nGTPase) domain is responsible for initiating mitochondrial trafficking and interactions with GCN1 in prostate cancer. The crystal structure of Miro1 nGTPase bound to GTP has been solved. However, no structural data is available for the nGTPase domain of Miro2. To better understand the similarities and differences in the functions of Miro1 and Miro2, we have initiated structural studies of Miro2. Here we report the backbone NMR chemical shift assignments of a 22 KDa construct of the nGTPase domain of Miro2 bound to GTP that includes residues 1-180 of the full-length protein. We affirm that the overall secondary structure of this complex closely resembles that of Miro1 nGTPase bound to GTP. Minor variations in the overall structures can be attributed to crystal packing interactions in the structure of Miro1. These NMR studies will form the foundation for future work identifying the specific interaction sites between Miro2 and its cellular binding partners.
    Keywords:  Backbone and sidechain nuclear magnetic resonance assignments; Chemical shifts; Miro2 N-terminal GTPase domain; Mitochondria; Solution state nuclear magnetic resonance
    DOI:  https://doi.org/10.1007/s12104-022-10103-5
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