Disease relevance of Polyribosomes

• The effect of a single injection of phenylalanine (2 mg/g of body weight) on brain polyribosomes, which increases the number of inactive monoribosomes, persists for 2 to 3 hours [1].
• FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association [2].
• In rats with chronic uremia (blood urea nitrogen greater than 45 mg/100 ml 1 mo after surgical reduction in renal mass), cell-free protein synthesis is reduced 30--40% in liver membrane-bound polyribosomes [3].
• Studies on the mechanism for entry of vesicular stomatitis virus glycoprotein G mRNA into membrane-bound polyribosome complexes [4].
• When Friend erythroleukemia cells were allowed to grow to stationary phase (2 X 10(6) to 3 X 10(6) cells per ml), approximately 60% of the mRNA for eucaryotic elongation factor Tu (eEF-Tu) sedimented at less than or equal to 80S, and most of the remaining factor mRNA was associated with small polysomes [5].

Psychiatry related information on Polyribosomes

• Here, we report that, following treatment with EDTA, Puralpha was released from polyribosomes in mRNA/protein complexes (mRNPs), which also contained mStaufen, Fragile X Mental Retardation Protein (FMRP), myosin Va, and other proteins with unknown functions [6].
• Haloperidol was able to block the increased locomotor activity due to drug dose and crowding at 1 mg/kg, and significatnly suppress disaggregation of brain polysomes in crowded animals [7].

High impact information on Polyribosomes

• Cofolding allosterically enhances association of eIF4E with the cap and is required for maintenance of optimal growth and polysome distributions in vivo [8].
• Despite equivalent cytoplasmic abundance, 251 mRNAs had an abnormal polyribosome profile in the absence of FMRP [9].
• Analysis of sucrose gradients for SIS1 protein shows that a large fraction of SIS1 is associated with 40S ribosomal subunits and the smaller polysomes [10].
• Moreover, in the absence of protein synthesis inhibitors, the tubulin RNAs that are lost from cells with elevated free tubulin subunit levels are those that are associated with polyribosomes [11].
• Puromycin and pactamycin, both of which remove RNAs from polysomes, completely unlink tubulin RNA content from the level of free subunits, whereas pretreatment of cells with cycloheximide, which traps mRNAs onto stalled polyribosomes, enhances the specific degradation of tubulin RNAs in response to increases in the subunit content [11].

Chemical compound and disease context of Polyribosomes

• 6-Thioguanine, at a dose of 40 mg/kg body weight, was administered to rats at 12 hr after partial hepatectomy; 6 hr later, liver polysomes and cell sap were isolated and utilized to measure the effects of this antimetabolite on protein synthesis in vitro [12].
• The size of the virus-specific mRNA isolated from polysomes of BHK-21 cells abortively infected with, or transformed by adenovirus type 12 was determined by electrophoresis in polyacrylamide gels in 98% formamide, i.e., under conditions which eliminated secondary structure or aggregation of RNA [13].
• Finally, the interaction between MA and EF1alpha impairs translation in vitro, a result consistent with a previously proposed model in which inhibition of translation by the accumulation of Gag serves to release viral RNA from polysomes, permitting the RNA to be packaged into nascent virions [14].
• Radiolabelled total RNA from each polyribosome population was fractionated in sucrose gradients into several pools or hybridized to intact adenovirus DNA to select virus-specific RNA [15].
• Cycloheximide prevents the disaggregation of brain polyribosomes induced by hypoglycemia, indicating that hypoglycemia affects brain protein synthesis, decreasing the rate of initiation relative to the rate of elongation of polypeptide chain synthesis [16].

Biological context of Polyribosomes

• FMRP is an RNA binding protein that associates with translating polyribosomes as part of a large messenger ribonucleoprotein (mRNP) and modulates the translation of its RNA ligands [17].
• The current study examined whether endonuclease-mediated mRNA decay involved the selective binding of PMR1 to substrate mRNA on polysomes [18].
• In order to determine the global effects of oncogenic Ras and Akt signaling pathways on translational efficiencies, we compared the gene expression profiles of total cellular mRNA and mRNA associated with polysomes [19].
• These data indicate that association of FMRP with polyribosomes must be functionally important and imply that the mechanism of the severe phenotype in the I304N patient lies in the sequestration of bound mRNAs in nontranslatable mRNP particles [2].
• Transfection of LacZ reporter constructs containing the utrophin 3'UTR showed that this region is critical for targeting chimeric mRNAs to cytoskeleton-bound polysomes and controlling transcript stability [20].

Anatomical context of Polyribosomes

• In sharp contrast, extraction with Triton leaves only radioactive skeletal proteins, which, although released from ribosomes, are near polyribosomes after a pulse [21].
• Histone mRNA, labeled with 32P or 3H-methionine during the S phase of partially synchronized HeLa cells, was isolated from the polyribosomes and purified as a "9S" component by sucrose gradient sedimentation [22].
• Most of the muscle-specific mRNAs were associated with polysomes in fused myotubes, whereas they were found in postpolysomal fractions in EGTA-treated cells [23].
• Nevertheless, we believe that in the cell, beta 2-microglobulin is synthesized in the rough endoplasmic reticulum, and that, because the protein is relatively small, the mRNA is released from the polyribosomes during the isolation procedure [24].
• Incorporation of radioactive methionine was exclusively associated with receptor in reticulocyte stroma, and nascent receptor was not detected on free polyribosomes [25].

Associations of Polyribosomes with chemical compounds

• These polysomes are released from the membrane upon treatment with puromycin and high salt [26].
• However, treatment of the cytoskeletal fraction with EDTA or low levels of ribonuclease resulted in polysome degradation but no release [27].
• Cytoplasmic RNA containing the sarc sequences has a sedimentation coefficient of 30S, is linked to polyadenylic acid and is present in polyribosomes in a form which can be released by treatment with EDTA [28].
• Detergent-washed nuclei are disrupted in 0.4 M ammonium sulfate, which also disociated contamination polysomes [29].
• A single injection of seven large neutral amino acids after phenylalanine administration results in a reversal of the effect on brain polyribosomes with a resultant decrease in monoribosomes to near normal levels [1].

Gene context of Polyribosomes

• SSL1 suppressor mutants that are conditional for growth have altered polysome profiles at the restrictive temperature, and their cell-free extracts are thermolabile in their ability to translate exogenously added mRNA [30].
• The dicistronic transcript is found in polysomes and the Adhr protein product is detected by antibody staining [31].
• FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex [32].
• In WT mouse brain, FMRP distributed with polysomes and granules [33].
• Dbp2p, like Upf1p, acts before or at decapping, is predominantly cytoplasmic, and associates with polyribosomes [34].

Analytical, diagnostic and therapeutic context of Polyribosomes

• Perfusion with acetaldehyde caused a similar decrease in albumin and urea synthesis, but did not cause polysome disaggregation [35].
• Northern blotting detected Fyn mRNA specifically in soluble polyribosomes and soluble Fyn protein was only detected shortly (1-2 min) after radiolabeling [36].
• Fractions from the heavy polysome region (1,000-2,000S) and fractions from the light polysome region (200-1,000S) were pooled separately, and the long-term labeled RNA was released by Sarkosyl/pronase and analysed by in situ hybridization [37].
• In addition, exogenously supplied myosin heavy chain mRNA is found associated with polysomes consisting of 4-10 ribosomes in myoblast cell cultures while in myotubes it is associated with very large polysomes, thus reflecting the different translational efficiencies that this message exhibits at two very different stages of myogenesis [38].
• The messenger RNA that specifies vitellogenin has been purified more than 800-fold from rooster liver polysomal RNA by a combination of methods, including immunoprecipitation of polysomes and chromatography of RNA on poly(U)-Sepharose [39].

References