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. 1995 Dec 15;14(24):6301–6310. doi: 10.1002/j.1460-2075.1995.tb00320.x

Cytoplasmic 3' poly(A) addition induces 5' cap ribose methylation: implications for translational control of maternal mRNA.

H Kuge 1, J D Richter 1
PMCID: PMC394754  PMID: 8557049

Abstract

During the early development of many animal species, the expression of new genetic information is governed by selective translation of stored maternal mRNAs. In many cases, this translational activation requires cytoplasmic poly(A) elongation. However, how this modification at the 3' end of an mRNA stimulates translation from the 5' end is unknown. Here we show that cytoplasmic polyadenylation stimulates cap ribose methylation during progesterone-induced oocyte maturation in Xenopus laevis. Translational recruitment of a chimeric reporter mRNA that is controlled by cytoplasmic polyadenylation coincides temporally with cap ribose methylation during this period. In addition, the inhibition of cap ribose methylation by S-isobutyladenosine significantly reduces translational activation of a reporter mRNA without affecting the increase of general protein synthesis or polyadenylation during maturation. These results provide evidence for a functional interaction between the termini of an mRNA molecule and suggest that 2'-O-ribose cap methylation mediates the translational recruitment of maternal mRNA.

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Selected References

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

  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ballantyne S., Bilger A., Astrom J., Virtanen A., Wickens M. Poly (A) polymerases in the nucleus and cytoplasm of frog oocytes: dynamic changes during oocyte maturation and early development. RNA. 1995 Mar;1(1):64–78. [PMC free article] [PubMed] [Google Scholar]
  3. Barbosa E., Moss B. mRNA(nucleoside-2'-)-methyltransferase from vaccinia virus. Characteristics and substrate specificity. J Biol Chem. 1978 Nov 10;253(21):7698–7702. [PubMed] [Google Scholar]
  4. Berleth T., Burri M., Thoma G., Bopp D., Richstein S., Frigerio G., Noll M., Nüsslein-Volhard C. The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo. EMBO J. 1988 Jun;7(6):1749–1756. doi: 10.1002/j.1460-2075.1988.tb03004.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bilger A., Fox C. A., Wahle E., Wickens M. Nuclear polyadenylation factors recognize cytoplasmic polyadenylation elements. Genes Dev. 1994 May 1;8(9):1106–1116. doi: 10.1101/gad.8.9.1106. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Caldwell D. C., Emerson C. P., Jr The role of cap methylation in the translational activation of stored maternal histone mRNA in sea urchin embryos. Cell. 1985 Sep;42(2):691–700. doi: 10.1016/0092-8674(85)90126-6. [DOI] [PubMed] [Google Scholar]
  8. DeLeon D. V., Cox K. H., Angerer L. M., Angerer R. C. Most early-variant histone mRNA is contained in the pronucleus of sea urchin eggs. Dev Biol. 1983 Nov;100(1):197–206. doi: 10.1016/0012-1606(83)90211-7. [DOI] [PubMed] [Google Scholar]
  9. Dworkin M. B., Shrutkowski A., Dworkin-Rastl E. Mobilization of specific maternal RNA species into polysomes after fertilization in Xenopus laevis. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7636–7640. doi: 10.1073/pnas.82.22.7636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fox C. A., Sheets M. D., Wickens M. P. Poly(A) addition during maturation of frog oocytes: distinct nuclear and cytoplasmic activities and regulation by the sequence UUUUUAU. Genes Dev. 1989 Dec;3(12B):2151–2162. doi: 10.1101/gad.3.12b.2151. [DOI] [PubMed] [Google Scholar]
  11. Fu L. N., Ye R. Q., Browder L. W., Johnston R. N. Translational potentiation of messenger RNA with secondary structure in Xenopus. Science. 1991 Feb 15;251(4995):807–810. doi: 10.1126/science.1990443. [DOI] [PubMed] [Google Scholar]
  12. Furuichi Y., LaFiandra A., Shatkin A. J. 5'-Terminal structure and mRNA stability. Nature. 1977 Mar 17;266(5599):235–239. doi: 10.1038/266235a0. [DOI] [PubMed] [Google Scholar]
  13. Furuichi Y., Shatkin A. J., Stavnezer E., Bishop J. M. Blocked, methylated 5'-terminal sequence in avian sarcoma virus RNA. Nature. 1975 Oct 16;257(5527):618–620. doi: 10.1038/257618a0. [DOI] [PubMed] [Google Scholar]
  14. Galili G., Kawata E. E., Smith L. D., Larkins B. A. Role of the 3'-poly(A) sequence in translational regulation of mRNAs in Xenopus laevis oocytes. J Biol Chem. 1988 Apr 25;263(12):5764–5770. [PubMed] [Google Scholar]
  15. Gallie D. R. The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency. Genes Dev. 1991 Nov;5(11):2108–2116. doi: 10.1101/gad.5.11.2108. [DOI] [PubMed] [Google Scholar]
  16. Gebauer F., Richter J. D. Cloning and characterization of a Xenopus poly(A) polymerase. Mol Cell Biol. 1995 Mar;15(3):1422–1430. doi: 10.1128/mcb.15.3.1422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gebauer F., Xu W., Cooper G. M., Richter J. D. Translational control by cytoplasmic polyadenylation of c-mos mRNA is necessary for oocyte maturation in the mouse. EMBO J. 1994 Dec 1;13(23):5712–5720. doi: 10.1002/j.1460-2075.1994.tb06909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gershon P. D., Moss B. Stimulation of poly(A) tail elongation by the VP39 subunit of the vaccinia virus-encoded poly(A) polymerase. J Biol Chem. 1993 Jan 25;268(3):2203–2210. [PubMed] [Google Scholar]
  19. Grossi de Sa M. F., Standart N., Martins de Sa C., Akhayat O., Huesca M., Scherrer K. The poly(A)-binding protein facilitates in vitro translation of poly(A)-rich mRNA. Eur J Biochem. 1988 Oct 1;176(3):521–526. doi: 10.1111/j.1432-1033.1988.tb14309.x. [DOI] [PubMed] [Google Scholar]
  20. Gurdon J. B. Changes in somatic cell nuclei inserted into growing and maturing amphibian oocytes. J Embryol Exp Morphol. 1968 Nov;20(3):401–414. [PubMed] [Google Scholar]
  21. Hake L. E., Richter J. D. CPEB is a specificity factor that mediates cytoplasmic polyadenylation during Xenopus oocyte maturation. Cell. 1994 Nov 18;79(4):617–627. doi: 10.1016/0092-8674(94)90547-9. [DOI] [PubMed] [Google Scholar]
  22. Hamm J., Mattaj I. W. Monomethylated cap structures facilitate RNA export from the nucleus. Cell. 1990 Oct 5;63(1):109–118. doi: 10.1016/0092-8674(90)90292-m. [DOI] [PubMed] [Google Scholar]
  23. Huarte J., Belin D., Vassalli A., Strickland S., Vassalli J. D. Meiotic maturation of mouse oocytes triggers the translation and polyadenylation of dormant tissue-type plasminogen activator mRNA. Genes Dev. 1987 Dec;1(10):1201–1211. doi: 10.1101/gad.1.10.1201. [DOI] [PubMed] [Google Scholar]
  24. Hyman L. E., Wormington W. M. Translational inactivation of ribosomal protein mRNAs during Xenopus oocyte maturation. Genes Dev. 1988 May;2(5):598–605. doi: 10.1101/gad.2.5.598. [DOI] [PubMed] [Google Scholar]
  25. Izaurralde E., Lewis J., McGuigan C., Jankowska M., Darzynkiewicz E., Mattaj I. W. A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell. 1994 Aug 26;78(4):657–668. doi: 10.1016/0092-8674(94)90530-4. [DOI] [PubMed] [Google Scholar]
  26. Konarska M. M., Padgett R. A., Sharp P. A. Recognition of cap structure in splicing in vitro of mRNA precursors. Cell. 1984 Oct;38(3):731–736. doi: 10.1016/0092-8674(84)90268-x. [DOI] [PubMed] [Google Scholar]
  27. Krainer A. R., Maniatis T., Ruskin B., Green M. R. Normal and mutant human beta-globin pre-mRNAs are faithfully and efficiently spliced in vitro. Cell. 1984 Apr;36(4):993–1005. doi: 10.1016/0092-8674(84)90049-7. [DOI] [PubMed] [Google Scholar]
  28. Krieg P. A., Melton D. A. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. doi: 10.1016/0076-6879(87)55027-3. [DOI] [PubMed] [Google Scholar]
  29. Kuge H., Inoue A. Maturation of Xenopus laevis oocyte by progesterone requires poly(A) tail elongation of mRNA. Exp Cell Res. 1992 Sep;202(1):52–58. doi: 10.1016/0014-4827(92)90403-u. [DOI] [PubMed] [Google Scholar]
  30. Laskey R. A., Mills A. D., Gurdon J. B., Partington G. A. Protein synthesis in oocytes of Xenopus laevis is not regulated by the supply of messenger RNA. Cell. 1977 Jun;11(2):345–351. doi: 10.1016/0092-8674(77)90051-4. [DOI] [PubMed] [Google Scholar]
  31. Lee R. C., Feinbaum R. L., Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993 Dec 3;75(5):843–854. doi: 10.1016/0092-8674(93)90529-y. [DOI] [PubMed] [Google Scholar]
  32. Legagneux V., Bouvet P., Omilli F., Chevalier S., Osborne H. B. Identification of RNA-binding proteins specific to Xenopus Eg maternal mRNAs: association with the portion of Eg2 mRNA that promotes deadenylation in embryos. Development. 1992 Dec;116(4):1193–1202. doi: 10.1242/dev.116.4.1193. [DOI] [PubMed] [Google Scholar]
  33. McGrew L. L., Dworkin-Rastl E., Dworkin M. B., Richter J. D. Poly(A) elongation during Xenopus oocyte maturation is required for translational recruitment and is mediated by a short sequence element. Genes Dev. 1989 Jun;3(6):803–815. doi: 10.1101/gad.3.6.803. [DOI] [PubMed] [Google Scholar]
  34. McGrew L. L., Richter J. D. Translational control by cytoplasmic polyadenylation during Xenopus oocyte maturation: characterization of cis and trans elements and regulation by cyclin/MPF. EMBO J. 1990 Nov;9(11):3743–3751. doi: 10.1002/j.1460-2075.1990.tb07587.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Muhlrad D., Decker C. J., Parker R. Deadenylation of the unstable mRNA encoded by the yeast MFA2 gene leads to decapping followed by 5'-->3' digestion of the transcript. Genes Dev. 1994 Apr 1;8(7):855–866. doi: 10.1101/gad.8.7.855. [DOI] [PubMed] [Google Scholar]
  36. Munns T. W., Oberst R. J., Sims H. F., Liszewski M. K. Antibody-nucleic acid complexes. Immunospecific recognition of 7-methylguanine- and N6-methyladenine-containing 5'-terminal oligonucleotides of mRNA. J Biol Chem. 1979 Jun 10;254(11):4327–4330. [PubMed] [Google Scholar]
  37. Murray A. W., Kirschner M. W. Cyclin synthesis drives the early embryonic cell cycle. Nature. 1989 May 25;339(6222):275–280. doi: 10.1038/339275a0. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Muthukrishnan S., Moss B., Cooper J. A., Maxwell E. S. Influence of 5'-terminal cap structure on the initiation of translation of vaccinia virus mRNA. J Biol Chem. 1978 Mar 10;253(5):1710–1715. [PubMed] [Google Scholar]
  40. Neuhard J., Randerath E., Randerath K. Ion-exchange thin-layer chromatography. 13. Resolution of complex nucleoside triphosphate mixtures. Anal Biochem. 1965 Nov;13(2):211–222. doi: 10.1016/0003-2697(65)90191-0. [DOI] [PubMed] [Google Scholar]
  41. O'Connor C. M., Germain B. J. Kinetic and electrophoretic analysis of transmethylation reactions in intact Xenopus laevis oocytes. J Biol Chem. 1987 Jul 25;262(21):10404–10411. [PubMed] [Google Scholar]
  42. Palatnik C. M., Wilkins C., Jacobson A. Translational control during early Dictyostelium development: possible involvement of poly(A) sequences. Cell. 1984 Apr;36(4):1017–1025. doi: 10.1016/0092-8674(84)90051-5. [DOI] [PubMed] [Google Scholar]
  43. Paris J., Philippe M. Poly(A) metabolism and polysomal recruitment of maternal mRNAs during early Xenopus development. Dev Biol. 1990 Jul;140(1):221–224. doi: 10.1016/0012-1606(90)90070-y. [DOI] [PubMed] [Google Scholar]
  44. Paris J., Richter J. D. Maturation-specific polyadenylation and translational control: diversity of cytoplasmic polyadenylation elements, influence of poly(A) tail size, and formation of stable polyadenylation complexes. Mol Cell Biol. 1990 Nov;10(11):5634–5645. doi: 10.1128/mcb.10.11.5634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Paris J., Swenson K., Piwnica-Worms H., Richter J. D. Maturation-specific polyadenylation: in vitro activation by p34cdc2 and phosphorylation of a 58-kD CPE-binding protein. Genes Dev. 1991 Sep;5(9):1697–1708. doi: 10.1101/gad.5.9.1697. [DOI] [PubMed] [Google Scholar]
  46. Plotch S. J., Bouloy M., Ulmanen I., Krug R. M. A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell. 1981 Mar;23(3):847–858. doi: 10.1016/0092-8674(81)90449-9. [DOI] [PubMed] [Google Scholar]
  47. Proweller A., Butler S. Efficient translation of poly(A)-deficient mRNAs in Saccharomyces cerevisiae. Genes Dev. 1994 Nov 1;8(21):2629–2640. doi: 10.1101/gad.8.21.2629. [DOI] [PubMed] [Google Scholar]
  48. Richter J. D., Smith L. D. Differential capacity for translation and lack of competition between mRNAs that segregate to free and membrane-bound polysomes. Cell. 1981 Nov;27(1 Pt 2):183–191. doi: 10.1016/0092-8674(81)90372-x. [DOI] [PubMed] [Google Scholar]
  49. Richter J. D. Translational control during early development. Bioessays. 1991 Apr;13(4):179–183. doi: 10.1002/bies.950130406. [DOI] [PubMed] [Google Scholar]
  50. Robert-Géro M., Lawrence F., Farrugia G., Berneman A., Blanchard P., Vigier P., Lederer E. Inhibition of virus-induced cell transformation by synthetic analogues of S-adenosyl homocysteine. Biochem Biophys Res Commun. 1975 Aug 18;65(4):1242–1249. doi: 10.1016/s0006-291x(75)80363-9. [DOI] [PubMed] [Google Scholar]
  51. Rosenthal E. T., Tansey T. R., Ruderman J. V. Sequence-specific adenylations and deadenylations accompany changes in the translation of maternal messenger RNA after fertilization of Spisula oocytes. J Mol Biol. 1983 May 25;166(3):309–327. doi: 10.1016/s0022-2836(83)80087-4. [DOI] [PubMed] [Google Scholar]
  52. Sachs A. B., Davis R. W., Kornberg R. D. A single domain of yeast poly(A)-binding protein is necessary and sufficient for RNA binding and cell viability. Mol Cell Biol. 1987 Sep;7(9):3268–3276. doi: 10.1128/mcb.7.9.3268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Sachs A. B., Davis R. W. The poly(A) binding protein is required for poly(A) shortening and 60S ribosomal subunit-dependent translation initiation. Cell. 1989 Sep 8;58(5):857–867. doi: 10.1016/0092-8674(89)90938-0. [DOI] [PubMed] [Google Scholar]
  54. Sachs A. B., Deardorff J. A. Translation initiation requires the PAB-dependent poly(A) ribonuclease in yeast. Cell. 1992 Sep 18;70(6):961–973. doi: 10.1016/0092-8674(92)90246-9. [DOI] [PubMed] [Google Scholar]
  55. Sagata N., Oskarsson M., Copeland T., Brumbaugh J., Vande Woude G. F. Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes. Nature. 1988 Oct 6;335(6190):519–525. doi: 10.1038/335519a0. [DOI] [PubMed] [Google Scholar]
  56. Sallés F. J., Lieberfarb M. E., Wreden C., Gergen J. P., Strickland S. Coordinate initiation of Drosophila development by regulated polyadenylation of maternal messenger RNAs. Science. 1994 Dec 23;266(5193):1996–1999. doi: 10.1126/science.7801127. [DOI] [PubMed] [Google Scholar]
  57. Schnierle B. S., Gershon P. D., Moss B. Cap-specific mRNA (nucleoside-O2'-)-methyltransferase and poly(A) polymerase stimulatory activities of vaccinia virus are mediated by a single protein. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2897–2901. doi: 10.1073/pnas.89.7.2897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Shatkin A. J. Capping of eucaryotic mRNAs. Cell. 1976 Dec;9(4 Pt 2):645–653. doi: 10.1016/0092-8674(76)90128-8. [DOI] [PubMed] [Google Scholar]
  59. Sheets M. D., Fox C. A., Hunt T., Vande Woude G., Wickens M. The 3'-untranslated regions of c-mos and cyclin mRNAs stimulate translation by regulating cytoplasmic polyadenylation. Genes Dev. 1994 Apr 15;8(8):926–938. doi: 10.1101/gad.8.8.926. [DOI] [PubMed] [Google Scholar]
  60. Sheets M. D., Wu M., Wickens M. Polyadenylation of c-mos mRNA as a control point in Xenopus meiotic maturation. Nature. 1995 Apr 6;374(6522):511–516. doi: 10.1038/374511a0. [DOI] [PubMed] [Google Scholar]
  61. Shimotohno K., Kodama Y., Hashimoto J., Miura K. I. Importance of 5'-terminal blocking structure to stabilize mRNA in eukaryotic protein synthesis. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2734–2738. doi: 10.1073/pnas.74.7.2734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Showman R. M., Leaf D. S., Anstrom J. A., Raff R. A. Translation of maternal histone mRNAs in sea urchin embryos: a test of control by 5' cap methylation. Dev Biol. 1987 May;121(1):284–287. doi: 10.1016/0012-1606(87)90161-8. [DOI] [PubMed] [Google Scholar]
  63. Simon R., Richter J. D. Further analysis of cytoplasmic polyadenylation in Xenopus embryos and identification of embryonic cytoplasmic polyadenylation element-binding proteins. Mol Cell Biol. 1994 Dec;14(12):7867–7875. doi: 10.1128/mcb.14.12.7867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Simon R., Tassan J. P., Richter J. D. Translational control by poly(A) elongation during Xenopus development: differential repression and enhancement by a novel cytoplasmic polyadenylation element. Genes Dev. 1992 Dec;6(12B):2580–2591. doi: 10.1101/gad.6.12b.2580. [DOI] [PubMed] [Google Scholar]
  65. Stebbins-Boaz B., Richter J. D. Multiple sequence elements and a maternal mRNA product control cdk2 RNA polyadenylation and translation during early Xenopus development. Mol Cell Biol. 1994 Sep;14(9):5870–5880. doi: 10.1128/mcb.14.9.5870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Vassalli J. D., Huarte J., Belin D., Gubler P., Vassalli A., O'Connell M. L., Parton L. A., Rickles R. J., Strickland S. Regulated polyadenylation controls mRNA translation during meiotic maturation of mouse oocytes. Genes Dev. 1989 Dec;3(12B):2163–2171. doi: 10.1101/gad.3.12b.2163. [DOI] [PubMed] [Google Scholar]
  67. Wasserman W. J., Richter J. D., Smith L. D. Protein synthesis during maturation promoting factor- and progesterone-induced maturation in Xenopus oocytes. Dev Biol. 1982 Jan;89(1):152–158. doi: 10.1016/0012-1606(82)90303-7. [DOI] [PubMed] [Google Scholar]
  68. Wickens M. In the beginning is the end: regulation of poly(A) addition and removal during early development. Trends Biochem Sci. 1990 Aug;15(8):320–324. doi: 10.1016/0968-0004(90)90022-4. [DOI] [PubMed] [Google Scholar]
  69. Wightman B., Ha I., Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993 Dec 3;75(5):855–862. doi: 10.1016/0092-8674(93)90530-4. [DOI] [PubMed] [Google Scholar]
  70. Wilt F. H. Polyadenylation of maternal RNA of sea urchin eggs after fertilization. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2345–2349. doi: 10.1073/pnas.70.8.2345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Winkler M. M., Nelson E. M., Lashbrook C., Hershey J. W. Multiple levels of regulation of protein synthesis at fertilization in sea urchin eggs. Dev Biol. 1985 Feb;107(2):290–300. doi: 10.1016/0012-1606(85)90312-4. [DOI] [PubMed] [Google Scholar]
  72. Wormington M. Poly(A) and translation: development control. Curr Opin Cell Biol. 1993 Dec;5(6):950–954. doi: 10.1016/0955-0674(93)90075-2. [DOI] [PubMed] [Google Scholar]
  73. Yang H., Moss M. L., Lund E., Dahlberg J. E. Nuclear processing of the 3'-terminal nucleotides of pre-U1 RNA in Xenopus laevis oocytes. Mol Cell Biol. 1992 Apr;12(4):1553–1560. doi: 10.1128/mcb.12.4.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Zelus B. D., Giebelhaus D. H., Eib D. W., Kenner K. A., Moon R. T. Expression of the poly(A)-binding protein during development of Xenopus laevis. Mol Cell Biol. 1989 Jun;9(6):2756–2760. doi: 10.1128/mcb.9.6.2756. [DOI] [PMC free article] [PubMed] [Google Scholar]

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