Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1991 Apr 15; 88(8): 3319–3323.

Oligopyrimidine tract at the 5' end of mammalian ribosomal protein mRNAs is required for their translational control.


Mammalian ribosomal protein (rp) mRNAs are subject to translational control, as illustrated by their selective release from polyribosomes in growth-arrested cells and their underrepresentation in polysomes in normally growing cells. In the present experiments, we have examined whether the translational control of rp mRNAs is attributable to the distinctive features of their 5' untranslated region, in particular to the oligopyrimidine tract adjacent to the cap structure. Murine lymphosarcoma cells were transfected with chimeric genes consisting of selected regions of rp mRNA fused to non-rp mRNA segments, and the translational efficiency of the resulting chimeric mRNAs was assessed in cells that either were growing normally or were growth-arrested by glucocorticoid treatment. We observed that translational control of rpL32 mRNA was abolished when its 5' untranslated region was replaced by that of beta-actin. At the same time, human growth hormone (hGH) mRNA acquired the typical behavior of rp mRNAs when it was preceded by the first 61 nucleotides of rpL30 mRNA or the first 29 nucleotides of rpS16 mRNA. Moreover, the translational control of rpS16-hGH mRNA was abolished by the substitution of purines into the pyrimidine tract or by shortening it from eight to six residues with a concomitant cytidine----uridine change at the 5' terminus. These results indicate that the 5'-terminal pyrimidine tract plays a critical role in the translational control mechanism. Possible factors that might interact with this translational cis regulatory element are discussed.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Mager WH. Control of ribosomal protein gene expression. Biochim Biophys Acta. 1988 Jan 25;949(1):1–15. [PubMed]
  • Steel LF, Jacobson A. Translational control of ribosomal protein synthesis during early Dictyostelium discoideum development. Mol Cell Biol. 1987 Mar;7(3):965–972. [PMC free article] [PubMed]
  • Al-Atia GR, Fruscoloni P, Jacobs-Lorena M. Translational regulation of mRNAs for ribosomal proteins during early Drosophila development. Biochemistry. 1985 Oct 8;24(21):5798–5803. [PubMed]
  • Amaldi F, Bozzoni I, Beccari E, Pierandrei-Amaldi P. Expression of ribosomal protein genes and regulation of ribosome biosynthesis in Xenopus development. Trends Biochem Sci. 1989 May;14(5):175–178. [PubMed]
  • Schmidt T, Chen PS, Pellegrini M. The induction of ribosome biosynthesis in a nonmitotic secretory tissue. J Biol Chem. 1985 Jun 25;260(12):7645–7650. [PubMed]
  • DePhilip RM, Rudert WA, Lieberman I. Preferential stimulation of ribosomal protein synthesis by insulin and in the absence of ribosomal and messenger ribonucleic acid formation. Biochemistry. 1980 Apr 15;19(8):1662–1669. [PubMed]
  • Ignotz GG, Hokari S, DePhilip RM, Tsukada K, Lieberman I. Lodish model and regulation of ribosomal protein synthesis by insulin-deficient chick embryo fibroblasts. Biochemistry. 1981 Apr 28;20(9):2550–2558. [PubMed]
  • Hammond ML, Bowman LH. Insulin stimulates the translation of ribosomal proteins and the transcription of rDNA in mouse myoblasts. J Biol Chem. 1988 Nov 25;263(33):17785–17791. [PubMed]
  • Agrawal MG, Bowman LH. Transcriptional and translational regulation of ribosomal protein formation during mouse myoblast differentiation. J Biol Chem. 1987 Apr 5;262(10):4868–4875. [PubMed]
  • Geyer PK, Meyuhas O, Perry RP, Johnson LF. Regulation of ribosomal protein mRNA content and translation in growth-stimulated mouse fibroblasts. Mol Cell Biol. 1982 Jun;2(6):685–693. [PMC free article] [PubMed]
  • Kaspar RL, Rychlik W, White MW, Rhoads RE, Morris DR. Simultaneous cytoplasmic redistribution of ribosomal protein L32 mRNA and phosphorylation of eukaryotic initiation factor 4E after mitogenic stimulation of Swiss 3T3 cells. J Biol Chem. 1990 Mar 5;265(7):3619–3622. [PubMed]
  • Meyuhas O, Thompson EA, Jr, Perry RP. Glucocorticoids selectively inhibit translation of ribosomal protein mRNAs in P1798 lymphosarcoma cells. Mol Cell Biol. 1987 Aug;7(8):2691–2699. [PMC free article] [PubMed]
  • Meyuhas O, Baldin V, Bouche G, Amalric F. Glucocorticoids repress ribosome biosynthesis in lymphosarcoma cells by affecting gene expression at the level of transcription, posttranscription and translation. Biochim Biophys Acta. 1990 May 24;1049(1):38–44. [PubMed]
  • Mariottini P, Bagni C, Annesi F, Amaldi F. Isolation and nucleotide sequences of cDNAs for Xenopus laevis ribosomal protein S8: similarities in the 5' and 3' untranslated regions of mRNAs for various r-proteins. Gene. 1988 Jul 15;67(1):69–74. [PubMed]
  • Mariottini P, Amaldi F. The 5' untranslated region of mRNA for ribosomal protein S19 is involved in its translational regulation during Xenopus development. Mol Cell Biol. 1990 Feb;10(2):816–822. [PMC free article] [PubMed]
  • Dudov KP, Perry RP. The gene family encoding the mouse ribosomal protein L32 contains a uniquely expressed intron-containing gene and an unmutated processed gene. Cell. 1984 Jun;37(2):457–468. [PubMed]
  • Wiedemann LM, Perry RP. Characterization of the expressed gene and several processed pseudogenes for the mouse ribosomal protein L30 gene family. Mol Cell Biol. 1984 Nov;4(11):2518–2528. [PMC free article] [PubMed]
  • Wagner M, Perry RP. Characterization of the multigene family encoding the mouse S16 ribosomal protein: strategy for distinguishing an expressed gene from its processed pseudogene counterparts by an analysis of total genomic DNA. Mol Cell Biol. 1985 Dec;5(12):3560–3576. [PMC free article] [PubMed]
  • Meyuhas O, Klein A. The mouse ribosomal protein L7 gene. Its primary structure and functional analysis of the promoter region. J Biol Chem. 1990 Jul 15;265(20):11465–11473. [PubMed]
  • Huxley C, Fried M. The mouse rpL7a gene is typical of other ribosomal protein genes in it's 5' region but differs in being located in a tight cluster of CpG-rich islands. Nucleic Acids Res. 1990 Sep 25;18(18):5353–5357. [PMC free article] [PubMed]
  • Kuzumaki T, Tanaka T, Ishikawa K, Ogata K. Rat ribosomal protein L35a multigene family: molecular structure and characterization of three L35a-related pseudogenes. Biochim Biophys Acta. 1987 Jul 14;909(2):99–106. [PubMed]
  • Chen IT, Roufa DJ. The transcriptionally active human ribosomal protein S17 gene. Gene. 1988 Oct 15;70(1):107–116. [PubMed]
  • Meyuhas O, Perry RP. Construction and identification of cDNA clones for mouse ribosomal proteins: application for the study of r-protein gene expression. Gene. 1980 Jul;10(2):113–129. [PubMed]
  • Schibler U, Kelley DE, Perry RP. Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. J Mol Biol. 1977 Oct 5;115(4):695–714. [PubMed]
  • Yenofsky R, Cereghini S, Krowczynska A, Brawerman G. Regulation of mRNA utilization in mouse erythroleukemia cells induced to differentiate by exposure to dimethyl sulfoxide. Mol Cell Biol. 1983 Jul;3(7):1197–1203. [PMC free article] [PubMed]
  • Makrides S, Chitpatima ST, Bandyopadhyay R, Brawerman G. Nucleotide sequence for a major messenger RNA for a 40 kilodalton polypeptide that is under translational control in mouse tumor cells. Nucleic Acids Res. 1988 Mar 25;16(5):2349–2349. [PMC free article] [PubMed]
  • Chitpatima ST, Makrides S, Bandyopadhyay R, Brawerman G. Nucleotide sequence of a major messenger RNA for a 21 kilodalton polypeptide that is under translational control in mouse tumor cells. Nucleic Acids Res. 1988 Mar 25;16(5):2350–2350. [PMC free article] [PubMed]
  • Chung S, Perry RP. Importance of introns for expression of mouse ribosomal protein gene rpL32. Mol Cell Biol. 1989 May;9(5):2075–2082. [PMC free article] [PubMed]
  • Nudel U, Zakut R, Shani M, Neuman S, Levy Z, Yaffe D. The nucleotide sequence of the rat cytoplasmic beta-actin gene. Nucleic Acids Res. 1983 Mar 25;11(6):1759–1771. [PMC free article] [PubMed]
  • Selden RF, Howie KB, Rowe ME, Goodman HM, Moore DD. Human growth hormone as a reporter gene in regulation studies employing transient gene expression. Mol Cell Biol. 1986 Sep;6(9):3173–3179. [PMC free article] [PubMed]
  • Hariharan N, Kelley DE, Perry RP. Equipotent mouse ribosomal protein promoters have a similar architecture that includes internal sequence elements. Genes Dev. 1989 Nov;3(11):1789–1800. [PubMed]
  • Hariharan N, Perry RP. A characterization of the elements comprising the promoter of the mouse ribosomal protein gene RPS16. Nucleic Acids Res. 1989 Jul 11;17(13):5323–5337. [PMC free article] [PubMed]
  • Hariharan N, Perry RP. Functional dissection of a mouse ribosomal protein promoter: significance of the polypyrimidine initiator and an element in the TATA-box region. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1526–1530. [PMC free article] [PubMed]
  • Cavannaugh AH, Thompson EA., Jr Hormonal regulation of transcription of rDNA. Inhibition of transcription during glucocorticoid-mediated inhibition of proliferation of lymphosarcoma P1798 cells in culture. J Biol Chem. 1983 Aug 25;258(16):9768–9773. [PubMed]
  • Grosschedl R, Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. [PubMed]
  • Minty AJ, Caravatti M, Robert B, Cohen A, Daubas P, Weydert A, Gros F, Buckingham ME. Mouse actin messenger RNAs. Construction and characterization of a recombinant plasmid molecule containing a complementary DNA transcript of mouse alpha-actin mRNA. J Biol Chem. 1981 Jan 25;256(2):1008–1014. [PubMed]
  • Chan YL, Lin A, McNally J, Wool IG. The primary structure of rat ribosomal protein L5. A comparison of the sequence of amino acids in the proteins that interact with 5 S rRNA. J Biol Chem. 1987 Sep 15;262(26):12879–12886. [PubMed]
  • Huang S, Hershey JW. Translational initiation factor expression and ribosomal protein gene expression are repressed coordinately but by different mechanisms in murine lymphosarcoma cells treated with glucocorticoids. Mol Cell Biol. 1989 Sep;9(9):3679–3684. [PMC free article] [PubMed]
  • Ng SY, Gunning P, Eddy R, Ponte P, Leavitt J, Shows T, Kedes L. Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Mol Cell Biol. 1985 Oct;5(10):2720–2732. [PMC free article] [PubMed]
  • Klausner RD, Harford JB. cis-trans models for post-transcriptional gene regulation. Science. 1989 Nov 17;246(4932):870–872. [PubMed]
  • Chitpatima ST, Brawerman G. Shifts in configuration of the 5'-noncoding region of a mouse messenger RNA under translational control. J Biol Chem. 1988 May 25;263(15):7164–7169. [PubMed]
  • Scherrer K. Prosomes, subcomplexes of untranslated mRNP. Mol Biol Rep. 1990 Feb;14(1):1–9. [PubMed]
  • Duncan R, Milburn SC, Hershey JW. Regulated phosphorylation and low abundance of HeLa cell initiation factor eIF-4F suggest a role in translational control. Heat shock effects on eIF-4F. J Biol Chem. 1987 Jan 5;262(1):380–388. [PubMed]
  • Walden WE, Godefroy-Colburn T, Thach RE. The role of mRNA competition in regulating translation. I. Demonstration of competition in vivo. J Biol Chem. 1981 Nov 25;256(22):11739–11746. [PubMed]
  • Sonenberg N. Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation. Prog Nucleic Acid Res Mol Biol. 1988;35:173–207. [PubMed]
  • Rhoads RE. Cap recognition and the entry of mRNA into the protein synthesis initiation cycle. Trends Biochem Sci. 1988 Feb;13(2):52–56. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...