Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2001 Dec;159(4):1617–1630. doi: 10.1093/genetics/159.4.1617

In Caenorhabditis elegans, the RNA-binding domains of the cytoplasmic polyadenylation element binding protein FOG-1 are needed to regulate germ cell fates.

S W Jin 1, N Arno 1, A Cohen 1, A Shah 1, Q Xu 1, N Chen 1, R E Ellis 1
PMCID: PMC1461887  PMID: 11779801

Abstract

FOG-1 controls germ cell fates in the nematode Caenorhabditis elegans. Sequence analyses revealed that FOG-1 is a cytoplasmic polyadenylation element binding (CPEB) protein; similar proteins from other species have been shown to bind messenger RNAs and regulate their translation. Our analyses of fog-1 mutations indicate that each of the three RNA-binding domains of FOG-1 is essential for activity. In addition, biochemical tests show that FOG-1 is capable of binding RNA sequences in the 3'-untranslated region of its own message. Finally, genetic assays reveal that fog-1 functions zygotically, that the small fog-1 transcript has no detectable function, and that missense mutations in fog-1 cause a dominant negative phenotype. This last observation suggests that FOG-1 acts in a complex, or as a multimer, to regulate translation. On the basis of these data, we propose that FOG-1 binds RNA to regulate germ cell fates and that it does so by controlling the translation of its targets. One of these targets might be the fog-1 transcript itself.

Full Text

The Full Text of this article is available as a PDF (513.5 KB).

Selected References

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

  1. Ahringer J., Rosenquist T. A., Lawson D. N., Kimble J. The Caenorhabditis elegans sex determining gene fem-3 is regulated post-transcriptionally. EMBO J. 1992 Jun;11(6):2303–2310. doi: 10.1002/j.1460-2075.1992.tb05289.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bally-Cuif L., Schatz W. J., Ho R. K. Characterization of the zebrafish Orb/CPEB-related RNA binding protein and localization of maternal components in the zebrafish oocyte. Mech Dev. 1998 Sep;77(1):31–47. doi: 10.1016/s0925-4773(98)00109-9. [DOI] [PubMed] [Google Scholar]
  3. Burd C. G., Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science. 1994 Jul 29;265(5172):615–621. doi: 10.1126/science.8036511. [DOI] [PubMed] [Google Scholar]
  4. Cali B. M., Anderson P. mRNA surveillance mitigates genetic dominance in Caenorhabditis elegans. Mol Gen Genet. 1998 Nov;260(2-3):176–184. doi: 10.1007/s004380050883. [DOI] [PubMed] [Google Scholar]
  5. Chang J. S., Tan L., Schedl P. The Drosophila CPEB homolog, orb, is required for oskar protein expression in oocytes. Dev Biol. 1999 Nov 1;215(1):91–106. doi: 10.1006/dbio.1999.9444. [DOI] [PubMed] [Google Scholar]
  6. Copeland P. R., Fletcher J. E., Carlson B. A., Hatfield D. L., Driscoll D. M. A novel RNA binding protein, SBP2, is required for the translation of mammalian selenoprotein mRNAs. EMBO J. 2000 Jan 17;19(2):306–314. doi: 10.1093/emboj/19.2.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Daròs J. A., Carrington J. C. RNA binding activity of NIa proteinase of tobacco etch potyvirus. Virology. 1997 Oct 27;237(2):327–336. doi: 10.1006/viro.1997.8802. [DOI] [PubMed] [Google Scholar]
  8. Dickson K. S., Bilger A., Ballantyne S., Wickens M. P. The cleavage and polyadenylation specificity factor in Xenopus laevis oocytes is a cytoplasmic factor involved in regulated polyadenylation. Mol Cell Biol. 1999 Aug;19(8):5707–5717. doi: 10.1128/mcb.19.8.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ding J., Hayashi M. K., Zhang Y., Manche L., Krainer A. R., Xu R. M. Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. Genes Dev. 1999 May 1;13(9):1102–1115. doi: 10.1101/gad.13.9.1102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ellis R. E., Kimble J. The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans. Genetics. 1995 Feb;139(2):561–577. doi: 10.1093/genetics/139.2.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Gebauer F., Richter J. D. Mouse cytoplasmic polyadenylylation element binding protein: an evolutionarily conserved protein that interacts with the cytoplasmic polyadenylylation elements of c-mos mRNA. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14602–14607. doi: 10.1073/pnas.93.25.14602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Graves L. E., Segal S., Goodwin E. B. TRA-1 regulates the cellular distribution of the tra-2 mRNA in C. elegans. Nature. 1999 Jun 24;399(6738):802–805. doi: 10.1038/21682. [DOI] [PubMed] [Google Scholar]
  14. Gray N. K., Wickens M. Control of translation initiation in animals. Annu Rev Cell Dev Biol. 1998;14:399–458. doi: 10.1146/annurev.cellbio.14.1.399. [DOI] [PubMed] [Google Scholar]
  15. Groisman I., Huang Y. S., Mendez R., Cao Q., Theurkauf W., Richter J. D. CPEB, maskin, and cyclin B1 mRNA at the mitotic apparatus: implications for local translational control of cell division. Cell. 2000 Oct 27;103(3):435–447. doi: 10.1016/s0092-8674(00)00135-5. [DOI] [PubMed] [Google Scholar]
  16. Hake L. E., Mendez R., Richter J. D. Specificity of RNA binding by CPEB: requirement for RNA recognition motifs and a novel zinc finger. Mol Cell Biol. 1998 Feb;18(2):685–693. doi: 10.1128/mcb.18.2.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Halloran N., Du Z., Wilson R. K. Sequencing reactions for the applied biosystems 373A Automated DNA Sequencer. Methods Mol Biol. 1993;23:297–315. doi: 10.1385/0-89603-248-5:297. [DOI] [PubMed] [Google Scholar]
  19. Hodgkin J., Papp A., Pulak R., Ambros V., Anderson P. A new kind of informational suppression in the nematode Caenorhabditis elegans. Genetics. 1989 Oct;123(2):301–313. doi: 10.1093/genetics/123.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Horvitz H. R., Brenner S., Hodgkin J., Herman R. K. A uniform genetic nomenclature for the nematode Caenorhabditis elegans. Mol Gen Genet. 1979 Sep;175(2):129–133. doi: 10.1007/BF00425528. [DOI] [PubMed] [Google Scholar]
  21. Jan E., Motzny C. K., Graves L. E., Goodwin E. B. The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans. EMBO J. 1999 Jan 4;18(1):258–269. doi: 10.1093/emboj/18.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jin S. W., Kimble J., Ellis R. E. Regulation of cell fate in Caenorhabditis elegans by a novel cytoplasmic polyadenylation element binding protein. Dev Biol. 2001 Jan 15;229(2):537–553. doi: 10.1006/dbio.2000.9993. [DOI] [PubMed] [Google Scholar]
  23. Jones A. R., Schedl T. Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68. Genes Dev. 1995 Jun 15;9(12):1491–1504. doi: 10.1101/gad.9.12.1491. [DOI] [PubMed] [Google Scholar]
  24. Kenan D. J., Query C. C., Keene J. D. RNA recognition: towards identifying determinants of specificity. Trends Biochem Sci. 1991 Jun;16(6):214–220. doi: 10.1016/0968-0004(91)90088-d. [DOI] [PubMed] [Google Scholar]
  25. Kraemer B., Crittenden S., Gallegos M., Moulder G., Barstead R., Kimble J., Wickens M. NANOS-3 and FBF proteins physically interact to control the sperm-oocyte switch in Caenorhabditis elegans. Curr Biol. 1999 Sep 23;9(18):1009–1018. doi: 10.1016/s0960-9822(99)80449-7. [DOI] [PubMed] [Google Scholar]
  26. Lantz V., Ambrosio L., Schedl P. The Drosophila orb gene is predicted to encode sex-specific germline RNA-binding proteins and has localized transcripts in ovaries and early embryos. Development. 1992 May;115(1):75–88. doi: 10.1242/dev.115.1.75. [DOI] [PubMed] [Google Scholar]
  27. Luitjens C., Gallegos M., Kraemer B., Kimble J., Wickens M. CPEB proteins control two key steps in spermatogenesis in C. elegans. Genes Dev. 2000 Oct 15;14(20):2596–2609. doi: 10.1101/gad.831700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mendez R., Murthy K. G., Ryan K., Manley J. L., Richter J. D. Phosphorylation of CPEB by Eg2 mediates the recruitment of CPSF into an active cytoplasmic polyadenylation complex. Mol Cell. 2000 Nov;6(5):1253–1259. doi: 10.1016/s1097-2765(00)00121-0. [DOI] [PubMed] [Google Scholar]
  29. Minshall N., Walker J., Dale M., Standart N. Dual roles of p82, the clam CPEB homolog, in cytoplasmic polyadenylation and translational masking. RNA. 1999 Jan;5(1):27–38. doi: 10.1017/s1355838299981220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mullis K., Faloona F., Scharf S., Saiki R., Horn G., Erlich H. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):263–273. doi: 10.1101/sqb.1986.051.01.032. [DOI] [PubMed] [Google Scholar]
  31. Pflugrad A., Meir J. Y., Barnes T. M., Miller D. M., 3rd The Groucho-like transcription factor UNC-37 functions with the neural specificity gene unc-4 to govern motor neuron identity in C. elegans. Development. 1997 May;124(9):1699–1709. doi: 10.1242/dev.124.9.1699. [DOI] [PubMed] [Google Scholar]
  32. Pulak R., Anderson P. mRNA surveillance by the Caenorhabditis elegans smg genes. Genes Dev. 1993 Oct;7(10):1885–1897. doi: 10.1101/gad.7.10.1885. [DOI] [PubMed] [Google Scholar]
  33. Puoti A., Kimble J. The Caenorhabditis elegans sex determination gene mog-1 encodes a member of the DEAH-Box protein family. Mol Cell Biol. 1999 Mar;19(3):2189–2197. doi: 10.1128/mcb.19.3.2189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Puoti A., Kimble J. The hermaphrodite sperm/oocyte switch requires the Caenorhabditis elegans homologs of PRP2 and PRP22. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3276–3281. doi: 10.1073/pnas.97.7.3276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Query C. C., Bentley R. C., Keene J. D. A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein. Cell. 1989 Apr 7;57(1):89–101. doi: 10.1016/0092-8674(89)90175-x. [DOI] [PubMed] [Google Scholar]
  36. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Stebbins-Boaz B., Cao Q., de Moor C. H., Mendez R., Richter J. D. Maskin is a CPEB-associated factor that transiently interacts with elF-4E. Mol Cell. 1999 Dec;4(6):1017–1027. doi: 10.1016/s1097-2765(00)80230-0. [DOI] [PubMed] [Google Scholar]
  39. Zhang B., Gallegos M., Puoti A., Durkin E., Fields S., Kimble J., Wickens M. P. A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature. 1997 Dec 4;390(6659):477–484. doi: 10.1038/37297. [DOI] [PubMed] [Google Scholar]
  40. de Moor C. H., Richter J. D. Cytoplasmic polyadenylation elements mediate masking and unmasking of cyclin B1 mRNA. EMBO J. 1999 Apr 15;18(8):2294–2303. doi: 10.1093/emboj/18.8.2294. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES