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Gene Review

45S  -  DNA segment, 45S

Mus musculus

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Disease relevance of 45S

  • In the presence of extracts from rapidly growing Ehrlich ascites cells, RNA polymerase I initiates specifically in that region of purified rDNA where the 5' end of 45S rRNA has been mapped [1].
  • When compared to the sedimentation rate of 29S rRNA, the RNAs of LDV and Sindbis virus sedimented at 48 and 45S, respectively, whether analyzed by zone sedimentation in sucrose density gradients containing low or high salt concentrations or denatured by treatment with formaldehyde [2].

High impact information on 45S

  • The size of the total RNA synthesized, determined by sedimentation on sucrose density gradients containing dimethylsulfoxide, ranged from less than 5S to 45S, and the size of the affinity-labeled sequences ranged from less than 5S to 28S [3].
  • Synthesis of the 45S rRNA by RNA polymerase I limits cell growth [4].
  • This spacer promoter is located about 2 kb upstream of the 45S pre-rRNA promoter and directs specific transcription initiations both in a cell-free system using truncated templates and in vivo after transfection into mouse cells [5].
  • The transcription initiation site of the human ribosomal RNA gene (rDNA) was located by using the single-strand specific nuclease protection method and by determining the first nucleotide of the in vitro capped 45S preribosomal RNA [6].
  • The first 19 nucleotides of these molecules appear identical--except for one mismatch--to the nucleotide sequence of the 5' end of a supposed early processing product of the mouse 45S RNA [6].

Biological context of 45S

  • Cloned ribosomal DNA (rDNA) from mouse, which contains the initiation site of 45S pre-rRNA transcription and 5' flanking sequences, has been used as the template in an in vitro transcription system [1].
  • Cleaved genomic DNAs from several mammalian species all exhibited strong dispersed hybridization with the SalI-P probes, and over 70% of the lambda clones in a mouse genomic library plus several selected clones containing globin, 45S rDNA, or 5S rDNA genes all formed hybrids with SalI-P [7].
  • Using the mTOR inhibitor rapamycin, we show that mTOR is required for the rapid and sustained serum-induced activation of 45S ribosomal gene transcription (rDNA transcription), a major rate-limiting step in ribosome biogenesis and cellular growth [8].
  • The transcription initiation site for rat 45S precursor ribosomal RNA synthesis was determined by nuclease protection mapping with two single-strand endonucleases [9].
  • Onset of polyoma-induced stimulation of 45S pre-rRNA synthesis was determined by hybridization of total cellular RNA with a plasmid (pMrSalB) containing the 5'-end of the mouse ribosomal gene and of the other cellular RNA species by standard biochemical analysis of cellular fractions [10].

Anatomical context of 45S

  • Mouse fibroblasts labeled 1-9 h with 3H-uridine contained radioactive 45S rRNA subspecies of 13.9, 13.3, and 12.8 kb, as determined by hybrid-selection with rDNA plasmids and by electrophoresis in agarose-formaldehyde [11].
  • The nucleotide sequence of a particular T1 oligonucleotide found in 41S and 28S RNAs of several cellular cell lines (human, mouse, rat and chicken fibroblast) but absent in 45S ribosomal RNA has been deduced [12].
  • Thus, one allele of the 45S rRNA spacer promoter is hypomethylated in sperm germ cells after Cr(III) exposure [13].
  • Here we report that exogenous angiogenin enhances the production of 45S rRNA in endothelial cells, and reduction of endogenous angiogenin inhibits its transcription [14].
  • The serum-induced transition of 3T3 cells from a resting to a growing state was accompanied by an early, apparently sequential stimulation of snRNA synthesis; stimulated synthesis of 7S, U1, U2, U3, U4 and U6 RNAs coincided in time with serum-induced stimulation of 45S pre-ribosomal RNA (pre-rRNA) and heterogeneous nuclear RNA (hnRNA) synthesis [15].

Associations of 45S with chemical compounds

  • As judges by sedimentation in SDS and in formamide gradients, the size of the RNA synthesized is heterogeneous from smaller than 10S to larger than 45S, thus resembling in vivo made RNA [16].
  • 45S RNA did not bear a triphosphate at the 5'-terminus, but various monophosphates are found [17].
  • (Y: pyrimidine nucleoside, Z: any nucleoside other than guanosine) These results suggest that a "transcribed spacer" sequence is present at the 3'-terminus of the 45S pre-ribosomal RNA, which is gradually removed during the steps of processing [18].
  • To inhibit selectively nucleolar transcription we used low concentrations of actinomycin D (act. D). Synthesis of 45S precursor- ribosomal RNA in mock- and polyoma-infected mouse kidney cells was completely blocked by 0.05 micrograms/ml act.D within 2 h [19].
  • On the other hand, inhibition of rRNA processing by the nucleoside analogs 5-fluoruridine and toyocamycin decreases the rate of 45S rRNA transcription in serum-stimulated cells but has no effect on the values found in resting cultures [20].

Physical interactions of 45S

  • Comparison of the terminal regional of 5.8S RNA with those of 18S RNA reveals differences which imply a more complex mechanism underlying the maturation of 45S precursor RNA than the finding of identical structure would have suggested [21].

Regulatory relationships of 45S

  • The results showed that polyoma-induced stimulation of cellular hnRNA (hnRNP) synthesis, the earliest presently known host cell reaction, preceded onset of stimulated 45S pre-rRNA synthesis and that the latter was paralleled by polyoma-induced stimulation of 5S RNA, tRNA and overall protein synthesis [10].

Other interactions of 45S

  • Sequence data and Southern analysis indicate an increase in 18S rDNA and 45S pre-rDNA methylation in uterine samples exposed prenatally to low and high doses of DES [22].


  1. Specific transcription of mouse ribosomal DNA in a cell-free system that mimics control in vivo. Grummt, I. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  2. Structure and chemical-physical characteristics of lactate dehydrogenase-elevating virus and its RNA. Brinton-Darnell, M., Plagemann, P.G. J. Virol. (1975) [Pubmed]
  3. Analysis of RNA initiated in isolated mouse myeloma nuclei using purine nucleoside 5'[gamma-S]triphosphates as affinity probes. Smith, M.M., Reeve, A.E., Huang, R.C. Cell (1978) [Pubmed]
  4. Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. Stefanovsky, V., Langlois, F., Gagnon-Kugler, T., Rothblum, L.I., Moss, T. Mol. Cell (2006) [Pubmed]
  5. A novel promoter in the mouse rDNA spacer is active in vivo and in vitro. Kuhn, A., Grummt, I. EMBO J. (1987) [Pubmed]
  6. Human ribosomal RNA gene: nucleotide sequence of the transcription initiation region and comparison of three mammalian genes. Financsek, I., Mizumoto, K., Mishima, Y., Muramatsu, M. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  7. A cytomegalovirus DNA sequence containing tracts of tandemly repeated CA dinucleotides hybridizes to highly repetitive dispersed elements in mammalian cell genomes. Jeang, K.T., Hayward, G.S. Mol. Cell. Biol. (1983) [Pubmed]
  8. mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Hannan, K.M., Brandenburger, Y., Jenkins, A., Sharkey, K., Cavanaugh, A., Rothblum, L., Moss, T., Poortinga, G., McArthur, G.A., Pearson, R.B., Hannan, R.D. Mol. Cell. Biol. (2003) [Pubmed]
  9. Identification and sequence of the initiation site for rat 45S ribosomal RNA synthesis. Harrington, C.A., Chikaraishi, D.M. Nucleic Acids Res. (1983) [Pubmed]
  10. Sequential stimulation of cellular RNA synthesis in polyoma-infected mouse kidney cell cultures. Matter, J.M., Tiercy, J.M., Weil, R. Nucleic Acids Res. (1983) [Pubmed]
  11. Characterization of mouse 45S ribosomal RNA subspecies suggests that the first processing cleavage occurs 600 +/- 100 nucleotides from the 5' end and the second 500 +/- 100 nucleotides from the 3' end of a 13.9 kb precursor. Gurney, T. Nucleic Acids Res. (1985) [Pubmed]
  12. Nucleotide sequence neighbouring a late modified guanylic residue within the 28S ribosomal RNA of several eukaryotic cells. Eladari, M.E., Hampe, A., Galibert, F. Nucleic Acids Res. (1977) [Pubmed]
  13. Allele-specific germ cell epimutation in the spacer promoter of the 45S ribosomal RNA gene after Cr(III) exposure. Shiao, Y.H., Crawford, E.B., Anderson, L.M., Patel, P., Ko, K. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
  14. The nuclear function of angiogenin in endothelial cells is related to rRNA production. Xu, Z.P., Tsuji, T., Riordan, J.F., Hu, G.F. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  15. Serum-induced stimulation of snRNA synthesis in mouse 3T3 fibroblasts. Tiercy, J.M., Weil, R. Experientia (1985) [Pubmed]
  16. Synthesis of messenger RNA-like molecules in isolated myeloma nuclei. Mory, Y.Y., Gefter, M.L. Nucleic Acids Res. (1977) [Pubmed]
  17. Heterogeneity of 5' -termini of nucleolar 45S, 32S and 28S RNA in mouse hepatoma. Kominami, R., Muramatsu, M. Nucleic Acids Res. (1977) [Pubmed]
  18. 3'-terminal processing of ribosomal RNA precursors in mammalian cells. Hamada, H., Kominami, R., Muramatsu, M. Nucleic Acids Res. (1980) [Pubmed]
  19. Polyoma-induced stimulation of nucleoplasmic transcription is paralleled by development of resistance against actinomycin D. Matter, J.M., Khandjian, E.W., Weil, R. Nucleic Acids Res. (1983) [Pubmed]
  20. Transcription of ribosomal RNA is differentially controlled in resting and growing BALB/c 3T3 cells. Perrone-Bizzozero, N., Iapalucci-Espinoza, S., Medrano, E.E., Franze-Fernández, M.T. J. Cell. Physiol. (1985) [Pubmed]
  21. Nucleotide sequence study of mouse 5.8S ribosomal RNA. Hampe, A., Eladari, M.E., Galibert, F. Biochimie (1976) [Pubmed]
  22. Uterine responsiveness to estradiol and DNA methylation are altered by fetal exposure to diethylstilbestrol and methoxychlor in CD-1 mice: effects of low versus high doses. Alworth, L.C., Howdeshell, K.L., Ruhlen, R.L., Day, J.K., Lubahn, D.B., Huang, T.H., Besch-Williford, C.L., vom Saal, F.S. Toxicol. Appl. Pharmacol. (2002) [Pubmed]
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