Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1976 Jan;73(1):19–23. doi: 10.1073/pnas.73.1.19

Inhibition of initiation of protein synthesis by 7-methylguanosine-5'-monophosphate.

E D Hickey, L A Weber, C Baglioni
PMCID: PMC335830  PMID: 1061116

Abstract

Translation of rabbit globin mRNA in a wheat germ protein-synthesizing system is inhibited by the nucleotide 7-methylguanosine-5'-monophosphate (m7G5'p) but not by other guanosine nucleotides without the 7-methyl group or with the phosphate in a different position. Translation of RNA of tobacco mosaic virus and poly(A) + HeLa RNA is also inhibited by m7G5'p. We show that m7G5'p prevents the association of mRNA with ribosomal subunits to form an initiation complex. We propose that m7G5'p interacts with a site on initiation factor(s) or ribosomes which is involved in mRNA recognition, presumably by binding to the 5'-terminal sequence m7G5'ppp. m7G5'p does not inhibit translation of poly(U) and RNA of satellite tobacco necrosis virus, which do not have the 5'-terminal sequence m7G5'ppp. In the case of RNA of satellite tobacco necrosis virus, some stimulation of its translation is consistently observed in the presence of m7G5'p; possible interpretations of this finding are discussed.

Full text

PDF
19

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham G., Rhodes D. P., Banerjee A. K. Novel initiation of RNA synthesis in vitro by vesicular stomatitis virus. Nature. 1975 May 1;255(5503):37–40. doi: 10.1038/255037a0. [DOI] [PubMed] [Google Scholar]
  2. Adams J. M., Cory S. Modified nucleosides and bizarre 5'-termini in mouse myeloma mRNA. Nature. 1975 May 1;255(5503):28–33. doi: 10.1038/255028a0. [DOI] [PubMed] [Google Scholar]
  3. Both G. W., Banerjee A. K., Shatkin A. J. Methylation-dependent translation of viral messenger RNAs in vitro. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1189–1193. doi: 10.1073/pnas.72.3.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Both G. W., Furuichi Y., Muthukrishnan S., Shatkin A. J. Ribosome binding to reovirus mRNA in protein synthesis requires 5' terminal 7-methylguanosine. Cell. 1975 Oct;6(2):185–195. doi: 10.1016/0092-8674(75)90009-4. [DOI] [PubMed] [Google Scholar]
  5. Darnbrough C., Legon S., Hunt T., Jackson R. J. Initiation of protein synthesis: evidence for messenger RNA-independent binding of methionyl-transfer RNA to the 40 S ribosomal subunit. J Mol Biol. 1973 May 25;76(3):379–403. doi: 10.1016/0022-2836(73)90511-1. [DOI] [PubMed] [Google Scholar]
  6. Furuichi Y., Miura K. A blocked structure at the 5' terminus of mRNA from cytoplasmic polyhedrosis virus. Nature. 1975 Jan 31;253(5490):374–375. doi: 10.1038/253374a0. [DOI] [PubMed] [Google Scholar]
  7. Furuichi Y., Morgan M., Shatkin A. J., Jelinek W., Salditt-Georgieff M., Darnell J. E. Methylated, blocked 5 termini in HeLa cell mRNA. Proc Natl Acad Sci U S A. 1975 May;72(5):1904–1908. doi: 10.1073/pnas.72.5.1904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Furuichi Y., Muthukrishnan S., Shatkin A. J. 5'-Terminal m-7G(5')ppp(5')G-m-p in vivo: identification in reovirus genome RNA. Proc Natl Acad Sci U S A. 1975 Feb;72(2):742–745. doi: 10.1073/pnas.72.2.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gaskill P., Kabat D. Unexpectedly large size of globin messenger ribonucleic acid. Proc Natl Acad Sci U S A. 1971 Jan;68(1):72–75. doi: 10.1073/pnas.68.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Horst J., Fraenkel-Conrat H., Mandeles S. Terminal heterogeneity at both ends of the satellite tobacco necrosis virus ribonucleic acid. Biochemistry. 1971 Dec 7;10(25):4748–4752. doi: 10.1021/bi00801a022. [DOI] [PubMed] [Google Scholar]
  11. Jacobs-Lorena, Baglioni C. Synthesis of rabbit globin by reticulocyte postribosomal supernatant and heterologous ribosomes. Eur J Biochem. 1973 Jun 15;35(3):559–565. doi: 10.1111/j.1432-1033.1973.tb02873.x. [DOI] [PubMed] [Google Scholar]
  12. Jacobs-Lorena M., Baglioni C. Messenger RNA for globin in the postribosomal supernatant of rabbit reticulocytes. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1425–1428. doi: 10.1073/pnas.69.6.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Keith J., Fraenkel-Conrat H. Tobacco mosaic virus RNA carries 5'-terminal triphosphorylated guanosine blocked by 5'-linked 7-methylguanosine. FEBS Lett. 1975 Sep 1;57(1):31–34. doi: 10.1016/0014-5793(75)80145-1. [DOI] [PubMed] [Google Scholar]
  14. Lesnaw J. A., Reichmann M. E. Identity of the 5'-terminal RNA nucleotide sequence of the satellite tobacco necrosis virus and its helper virus: possible role of the 5'-terminus in the recognition by virus-specific RNA replicase. Proc Natl Acad Sci U S A. 1970 May;66(1):140–145. doi: 10.1073/pnas.66.1.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Muthukrishnan S., Both G. W., Furuichi Y., Shatkin A. J. 5'-Terminal 7-methylguanosine in eukaryotic mRNA is required for translation. Nature. 1975 May 1;255(5503):33–37. doi: 10.1038/255033a0. [DOI] [PubMed] [Google Scholar]
  16. Pemberton R. E., Liberti P., Baglioni C. Isolation of messenger RNA from polysomes by chromatography on oligo(dT)-cellulose. Anal Biochem. 1975 May 26;66(1):18–28. doi: 10.1016/0003-2697(75)90720-4. [DOI] [PubMed] [Google Scholar]
  17. Roberts B. E., Paterson B. M. Efficient translation of tobacco mosaic virus RNA and rabbit globin 9S RNA in a cell-free system from commercial wheat germ. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2330–2334. doi: 10.1073/pnas.70.8.2330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Roberts B. E. Tobacco mosaic virus RNA directs the synthesis of a coat protein peptide in a cell-free system from wheat. J Mol Biol. 1973 Nov 15;80(4):733–742. doi: 10.1016/0022-2836(73)90206-4. [DOI] [PubMed] [Google Scholar]
  19. Rottman F., Shatkin A. J., Perry R. P. Sequences containing methylated nucleotides at the 5' termini of messenger RNAs: possible implications for processing. Cell. 1974 Nov;3(3):197–199. doi: 10.1016/0092-8674(74)90131-7. [DOI] [PubMed] [Google Scholar]
  20. Wei C. M., Moss B. Methylated nucleotides block 5'-terminus of vaccinia virus messenger RNA. Proc Natl Acad Sci U S A. 1975 Jan;72(1):318–322. doi: 10.1073/pnas.72.1.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wimmer E., Reichmann M. E. Pyrophosphate in the 5' terminal position of a viral ribonucleic acid. Science. 1968 Jun 28;160(3835):1452–1454. doi: 10.1126/science.160.3835.1452. [DOI] [PubMed] [Google Scholar]
  22. Zimmern D. The 5' end group of tobacco mosaic virus RNA is m7G5' ppp5' Gp. Nucleic Acids Res. 1975 Jul;2(7):1189–1201. doi: 10.1093/nar/2.7.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES