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Disease relevance of Polyribosomes


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


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


  1. Hyperphenylalanemia: effect on brain polyribosomes can be partially reversed by other amino acids. Hughes, J.V., Johnson, T.C. Science (1977) [Pubmed]
  2. FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association. Feng, Y., Absher, D., Eberhart, D.E., Brown, V., Malter, H.E., Warren, S.T. Mol. Cell (1997) [Pubmed]
  3. Influence of chronic renal failure on protein synthesis and albumin metabolism in rat liver. Grossman, S.B., Yap, S.H., Shafritz, D.A. J. Clin. Invest. (1977) [Pubmed]
  4. Studies on the mechanism for entry of vesicular stomatitis virus glycoprotein G mRNA into membrane-bound polyribosome complexes. Grubman, M.J., Weinstein, J.A., Shafritz, D.A. J. Cell Biol. (1977) [Pubmed]
  5. Regulation of the utilization of mRNA for eucaryotic elongation factor Tu in Friend erythroleukemia cells. Rao, T.R., Slobin, L.I. Mol. Cell. Biol. (1987) [Pubmed]
  6. Identification of mRNA/protein (mRNP) complexes containing Puralpha, mStaufen, fragile X protein, and myosin Va and their association with rough endoplasmic reticulum equipped with a kinesin motor. Ohashi, S., Koike, K., Omori, A., Ichinose, S., Ohara, S., Kobayashi, S., Sato, T.A., Anzai, K. J. Biol. Chem. (2002) [Pubmed]
  7. Effect of crowding on amphetamine-induced disaggregation of brain polyribosomes. Blackshear, M.A., Wade, L.H., Proctor, C.D. Archives internationales de pharmacodynamie et de thérapie. (1979) [Pubmed]
  8. Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Gross, J.D., Moerke, N.J., von der Haar, T., Lugovskoy, A.A., Sachs, A.B., McCarthy, J.E., Wagner, G. Cell (2003) [Pubmed]
  9. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Brown, V., Jin, P., Ceman, S., Darnell, J.C., O'Donnell, W.T., Tenenbaum, S.A., Jin, X., Feng, Y., Wilkinson, K.D., Keene, J.D., Darnell, R.B., Warren, S.T. Cell (2001) [Pubmed]
  10. The yeast SIS1 protein, a DnaJ homolog, is required for the initiation of translation. Zhong, T., Arndt, K.T. Cell (1993) [Pubmed]
  11. Autoregulation of tubulin expression is achieved through specific degradation of polysomal tubulin mRNAs. Pachter, J.S., Yen, T.J., Cleveland, D.W. Cell (1987) [Pubmed]
  12. Effects of 6-thioguanine on RNA biosynthesis in regenerating rat liver. Carrico, C.K., Sartorelli, A.C. Cancer Res. (1977) [Pubmed]
  13. Transcription of the genome of adenovirus type 12. I. Viral mRNA in abortively infected and transformed cells. Ortin, J., Doerfler, W. J. Virol. (1975) [Pubmed]
  14. Translation elongation factor 1-alpha interacts specifically with the human immunodeficiency virus type 1 Gag polyprotein. Cimarelli, A., Luban, J. J. Virol. (1999) [Pubmed]
  15. Differences in sequence content of nuclear and cytoplasmic polyribosomal RNA from adenovirus-infected cells. Chatterjee, N.K., Tuchowski, C., Eagan, G.E., Haley, T.M. Biochem. J. (1984) [Pubmed]
  16. Effects of hypoglycemia on rat brain polyribosome sedimentation pattern. Ulovec, Z., Narancsik, P., Gamulin, S. J. Neurochem. (1985) [Pubmed]
  17. A decade of molecular studies of fragile X syndrome. O'Donnell, W.T., Warren, S.T. Annu. Rev. Neurosci. (2002) [Pubmed]
  18. Endonuclease-mediated mRNA decay involves the selective targeting of PMR1 to polyribosome-bound substrate mRNA. Yang, F., Schoenberg, D.R. Mol. Cell (2004) [Pubmed]
  19. Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes. Rajasekhar, V.K., Viale, A., Socci, N.D., Wiedmann, M., Hu, X., Holland, E.C. Mol. Cell (2003) [Pubmed]
  20. Distinct regions in the 3' untranslated region are responsible for targeting and stabilizing utrophin transcripts in skeletal muscle cells. Gramolini, A.O., Bélanger, G., Jasmin, B.J. J. Cell Biol. (2001) [Pubmed]
  21. The spatial distribution of polyribosomes in 3T3 cells and the associated assembly of proteins into the skeletal framework. Fulton, A.B., Wan, K.M., Penman, S. Cell (1980) [Pubmed]
  22. Histone mRNAs contain blocked and methylated 5' terminal sequences but lack methylated nucleosides at internal positions. Moss, B., Gershowitz, A., Weber, L.A., Baglioni, C. Cell (1977) [Pubmed]
  23. Three types of muscle-specific gene expression in fusion-blocked rat skeletal muscle cells: translational control in EGTA-treated cells. Endo, T., Nadal-Ginard, B. Cell (1987) [Pubmed]
  24. Synthesis of HLA antigens from membrane-associated messenger RNA. Lee, J.S., Trowsdale, J., Bodmer, W.F. J. Exp. Med. (1980) [Pubmed]
  25. Biosynthesis of the transferrin receptor in rabbit reticulocytes. Cox, T.M., O'Donnell, M.W., Aisen, P., London, I.M. J. Clin. Invest. (1985) [Pubmed]
  26. How a single Sindbis virus mRNA directs the synthesis of one soluble protein and two integral membrane glycoproteins. Wirth, D.F., Katz, F., Small, B., Lodish, H.F. Cell (1977) [Pubmed]
  27. Translational initiation factor and ribosome association with the cytoskeletal framework fraction from HeLa cells. Howe, J.G., Hershey, J.W. Cell (1984) [Pubmed]
  28. Characteristics of cellular RNA related to the transforming gene of avian sarcoma viruses. Spector, D.H., Baker, B., Varmus, H.E., Bishop, J.M. Cell (1978) [Pubmed]
  29. Message and non-message sequences adjacent to poly(A) in steady state heterogeneous nuclear RNA of HeLa cells. Herman, R.C., Williams, J.G., Penman, S. Cell (1976) [Pubmed]
  30. SSL1, a suppressor of a HIS4 5'-UTR stem-loop mutation, is essential for translation initiation and affects UV resistance in yeast. Yoon, H., Miller, S.P., Pabich, E.K., Donahue, T.F. Genes Dev. (1992) [Pubmed]
  31. The Adh-related gene of Drosophila melanogaster is expressed as a functional dicistronic messenger RNA: multigenic transcription in higher organisms. Brogna, S., Ashburner, M. EMBO J. (1997) [Pubmed]
  32. A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P. Schenck, A., Bardoni, B., Moro, A., Bagni, C., Mandel, J.L. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  33. The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain. Aschrafi, A., Cunningham, B.A., Edelman, G.M., Vanderklish, P.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  34. Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing. Bond, A.T., Mangus, D.A., He, F., Jacobson, A. Mol. Cell. Biol. (2001) [Pubmed]
  35. Alcohol, amino acids, and albumin synthesis. III. Effects of ethanol, acetaldehyde, and 4-methylpyrazole. Oratz, M., Rothschild, M.A., Schreiber, S.S. Gastroenterology (1978) [Pubmed]
  36. Rapid plasma membrane anchoring of newly synthesized p59fyn: selective requirement for NH2-terminal myristoylation and palmitoylation at cysteine-3. van't Hof, W., Resh, M.D. J. Cell Biol. (1997) [Pubmed]
  37. Demonstration of Balbiani ring RNA sequences in polysomes. Wieslander, L., Daneholt, B. J. Cell Biol. (1977) [Pubmed]
  38. Uptake and utilization of mRNA by myogenic cells in culture. Mroczkowski, B., Dym, H.P., Siegel, E.J., Heywood, S.M. J. Cell Biol. (1980) [Pubmed]
  39. Effect of estrogen on gene expression: purification of vitellogenin messenger RNA. Wetekam, W., Mullinix, K.P., Deeley, R.G., Kronenberg, H.M., Eldridge, J.D., Meyers, M., Goldberger, R.F. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
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