Disease relevance of Ribosomes

• Crystal structures of H. marismortui large ribosomal subunits containing the mutation G2099A (A2058 in E. coli) with erythromycin, azithromycin, clindamycin, virginiamycin S, and telithromycin bound explain why eubacterial ribosomes containing the mutation A2058G are resistant to them [1].
• Here, we show that ribosome frameshifting at a specific tryptophan codon during Trp-tRNA limitation accounts for suppression of a group of downstream frameshift alleles in the rIIB gene of bacteriophage T4 [2].
• Patients with rheumatoid arthritis and chronic active hepatitis manifested a lower incidence and titer of antibodies to ribosomes, whereas serums from normal individuals and from patients with sarcoidosis, chronic glomerulonephritis, and malignant tumors showed no significant reactivity with cytoplasmic ribosomes [3].
• Translation by ribosome shunting on adenovirus and hsp70 mRNAs facilitated by complementarity to 18S rRNA [4].
• Here we present evidence that a nuclear form of Notch2 corresponding to the biologically active intracellular domain (N2ICD) is expressed from this recombinant retrovirus through internal ribosome entry [5].

Psychiatry related information on Ribosomes

• Dendritic localization, which was confirmed by co-fractionation of FMRP with synaptosomal ribosomes, suggests a possible role of FMRP in the translation of proteins involved in dendritic structure or function and relevant for the mental retardation occurring in fragile X syndrome [6].
• There is clearly a burst of ribosome synthesis starting as early as 30 min after copulation and declining after 6 h [7].

High impact information on Ribosomes

• Part of the additional binding energy of cognate tRNA is used to induce conformational changes in the ribosome that stabilize a transition state for GTP hydrolysis by EF-Tu and subsequently result in accelerated accommodation of tRNA into the peptidyl transferase center [8].
• The ribosome discriminates between correct and incorrect aminoacyl-tRNAs (aa-tRNAs), or their complexes with elongation factor Tu (EF-Tu) and GTP, according to the match between anticodon and mRNA codon in the A site [9].
• eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation [10].
• Eukaryotic translation initiation factor 4F (eIF4F) is a protein complex that mediates recruitment of ribosomes to mRNA [10].
• Unique tRNAs that have complementary UCA anticodons are aminoacylated with serine, the seryl-tRNA is converted to selenocysteyl-tRNA and the latter binds specifically to a special elongation factor and is delivered to the ribosome [11].

Chemical compound and disease context of Ribosomes

• When the "fragment reaction" was used as a model assay for peptide bond formation, Escherichia coli ribosomes or 50S subunits retained 20 to 40 percent activity after extensive treatment with proteinase K and SDS, but lost activity after extraction with phenol or exposure to EDTA [12].
• E. coli ribosomes with a C912 to U base change in the 16S rRNA are streptomycin resistant [13].
• A major difference in the binding site for these antibiotics between prokaryotic and eukaryotic ribosomes is the identity of the nucleotide at position 1408 (Escherichia coli numbering), which is an adenosine in prokaryotic ribosomes and a guanosine in eukaryotic ribosomes [14].
• Here we show that a conserved arginine, R29, of Escherichia coli EF-G is crucial for GTP hydrolysis on the ribosome, but not for GTP binding or ribosome interaction, suggesting that it may be directly involved in catalysis [15].
• When membrane-polysome complexes from Escherichia coli were treated with puromycin, at various Mg2+ and K+ concentrations, the bulk of the ribosomes were released from the membrane [16].

Biological context of Ribosomes

• We discuss the properties of the overlapping gene in relation to its lysis function, recognition of the lysis initiator region by E. coli versus eucaryotic ribosomes and op3 as a ribosome binding site mutant for the f2 synthetase cistron [17].
• We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1) [18].
• We have extended these studies to show that the phenomenon of drug adaptation in Tetrahymena, at least with respect to cycloheximide, is associated with this ribosome phosphorylation [19].
• The steady-state translational activation of the GCN4 mRNA is based upon an increase in the rate of ribosome initiation at the protein coding AUG following translation of the 5' most proximal open reading frame located in its untranslated region [20].
• These suppressor mutations reduce the ribosome affinity of eIF5B and increase AUG skipping/leaky scanning [21].

Anatomical context of Ribosomes

• Unspliced HAC1 mRNA is stable, located in the cytosol, and is associated with polyribosomes, yet does not produce protein, indicating that the ribosomes engaged on the mRNA are stalled [22].
• The mRNA for the viral glycoprotein (G), known to translate only on ribosomes bound to endoplasmic reticulum, is also retained by the detergent-extracted structure [23].
• Binding of bromouridine-substituted reovirus mRNA to ribosomes was inhibited to the greatest extent, while binding of inosine-substituted reovirus mRNA was not inhibited at all in the reticulocyte lysate system or was slightly inhibited in a wheat-germ system [24].
• The division of labor between RNA and protein illustrated by this simple system reveals principles applicable to complex ribonucleoprotein assemblies such as the spliceosome and ribosome [25].
• Explanations have included the use by mitochondria of codons requiring a specialized tRNA population and the fortuitous occurrence within genes of purine-rich sequences resembling bacterial ribosome binding sites [26].

Associations of Ribosomes with chemical compounds

• While pre-steady-state kinetic analysis of the peptidyl transferase activity of the mutant ribosomes reveals substantially reduced rates of peptide bond formation using the minimal substrate puromycin, their rates of peptide bond formation are unaffected when the substrates are intact aminoacyl-tRNAs [27].
• The isolation of a class of partial revertants to temperature insensitivity which have simultaneously become sensitive to streptomycin suggests that the translational requirement for the anticodon modification can be partially overcome by a change in the structure of the ribosome [28].
• We propose that reduced elongation rates in the presence of cycloheximide allow otherwise insufficient SRP to interact efficiently with ribosomes [29].
• Questioning of reported evidence for guanosine tetraphosphate synthesis in a ribosome system from mouse embryos [30].
• The adaptive response to nutritional stress involves increased translation of the arginine/lysine transporter (cat-1) mRNA via an internal ribosome entry site (IRES) within the mRNA leader [31].

Gene context of Ribosomes

• Constructions were characterized that allow ribosomes to stop selectively before, within or downstream from the galK initiation signal [32].
• A yeast gene homologous to bacterial RNase III (RNT1) encodes a double-strand-specific endoribonuclease essential for ribosome synthesis [33].
• We show that the polysomal, cytoplasmic pool of HAC1 mRNA is a substrate for splicing, suggesting that the stalled ribosomes may resume translation after the intron is removed [22].
• Our interpretation is that this short sequence represents a common signal that must be recognized by the box7-encoded mRNA maturase, in conjunction with the mitochondrial ribosome, to splice out the introns in the two nonhomologous genes, cob-box and oxi3 [34].
• The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator [35].

Analytical, diagnostic and therapeutic context of Ribosomes

• Both ribosome isolation by centrifugation through sucrose cushions and immunoprecipitation with anti-puromycin antibodies demonstrated that the photoadducts form on ribosome-bound polypeptides [36].
• Two distinct classes of vesicles could be isolated by density gradient centrifugation from microsomes treated with 0.16% Triton X-100: one with ribosomes bound to the inner membrane surfaces ("inverted rough" vesicles) and another with no ribosomes attached to the membranes [37].
• We located the polypeptide nascent chain as it leaves cytoplasmic ribosomes from the plant Lemna gibba by immune electron microscopy using antibodies against the small subunit of the enzyme ribulose-1,5-bisphosphate carboxylase [38].
• Cryo-electron microscopy has been used to visualize elongation factor G (EF-G) on the 70S ribosome in GDP and GTP states [39].
• Placebo or VEGF +/- internal ribosome entry site (IRES) was continuously administrated perimuscularly in the ischemic zone by using an infusion pump [40].

References