A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans

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Messenger RNA regulation is a critical mode of controlling gene expression. Regulation of mRNA stability and translation is linked to controls of poly(A) tail length1,2. Poly(A) lengthening can stabilize and translationally activate mRNAs, whereas poly(A) removal can trigger degradation and translational repression. Germline granules (for example, polar granules in flies, P granules in worms) are ribonucleoprotein particles implicated in translational control3. Here we report that the Caenorhabditis elegans gene gld-2, a regulator of mitosis/meiosis decision and other germline events4, encodes the catalytic moiety of a cytoplasmic poly(A) polymerase (PAP) that is associated with P granules in early embryos. Importantly, the GLD-2 protein sequence has diverged substantially from that of conventional eukaryotic PAPs, and lacks a recognizable RRM (RNA recognition motif)-like domain. GLD-2 has little PAP activity on its own, but is stimulated in vitro by GLD-3. GLD-3 is also a developmental regulator, and belongs to the Bicaudal-C family of RNA binding proteins5. We suggest that GLD-2 is the prototype for a class of regulatory cytoplasmic PAPs that are recruited to specific mRNAs by a binding partner, thereby targeting those mRNAs for polyadenylation and increased expression.

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Figure 1: The gld-2 gene and its transcripts.
Figure 2: GLD-2 belongs to the polymerase β nucleotidyltransferase superfamily.
Figure 3: The GLD-2 protein.
Figure 4: GLD-2/GLD-3 is a new type of poly(A) polymerase.
Figure 5: Model for architecture of GLD-2/GLD-3 rcPAP enzyme.


  1. 1

    Richter, J. D. in Translational Control of Gene Expression (eds Sonenberg, N., Hershey, J. W. B. & Mathews, M. B.) 785–805 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2000)

  2. 2

    Wickens, M., Goodwin, E. B., Kimble, J., Strickland, S. & Hentze, M. W. in Translational Control of Gene Expression (eds Sonenberg, N., Hershey, J. W. B. & Mathews, M. B.) 295–370 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2000)

  3. 3

    Seydoux, G. & Strome, S. Launching the germline in Caenorhabditis elegans: regulation of gene expression in early germ cells. Development 126, 3275–3283 (1999)

  4. 4

    Kadyk, L. C. & Kimble, J. Genetic regulation of entry into meiosis in Caenorhabditis elegans. Development 125, 1803–1813 (1998)

  5. 5

    Eckmann, C., Kraemer, B., Wickens, M. & Kimble, J. GLD-3, a Bicaudal-C homolog that represses FBF to control germline sex determination in C. elegans. Dev. Cell (in the press)

  6. 6

    Holm, L. & Sander, C. DNA polymerase β belongs to an ancient nucleotidyltransferase superfamily. Trends Biochem. Sci. 20, 345–347 (1995)

  7. 7

    Aravind, L. & Koonin, E. V. DNA polymerase β-like nucleotidyltransferase superfamily: identification of three new families, classification and evolutionary history. Nucleic Acids Res. 27, 1609–1618 (1999)

  8. 8

    Martin, G., Keller, W. & Doublie, W. Crystal structure of mammalian poly(A) polymerase in complex with an analog of ATP. EMBO J. 19, 4193–4203 (2000)

  9. 9

    Bard, J. et al. Structure of yeast poly(A) polymerase alone and in complex with 3′-dATP. Science 289, 1346–1349 (2000)

  10. 10

    Kawasaki, I. et al. PGL-1, a predicted RNA-binding component of germ granules, is essential for fertility in C. elegans. Cell 94, 635–645 (1998)

  11. 11

    Praitis, V., Casey, E., Collar, D. & Austin, J. Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. Genetics 157, 1217–1226 (2001)

  12. 12

    Colgan, D. F. & Manley, J. L. Mechanism and regulation of mRNA polyadenylation. Genes Dev. 11, 2755–2766 (1997)

  13. 13

    Kashiwabara, S.-i. et al. Identification of a novel isoform of poly(A) polymerase, TPAP, specifically present in the cytoplasm of spermatogenic cells. Dev. Biol. 228, 106–115 (2000)

  14. 14

    Kyriakopoulou, C. B., Nordvarg, H. & Virtanen, A. A novel nuclear human poly(A) polymerase (PAP), PAPγ. J. Biol. Chem. 276, 33504–33511 (2001)

  15. 15

    Topalian, S. L. et al. Identification and functional characterization of neo-poly(A) polymerase, an RNA processing enzyme overexpressed in human tumors. Mol. Cell. Biol. 21, 5614–5623 (2001)

  16. 16

    Subramaniam, K. & Seydoux, G. nos-1 and nos-2, two genes related to Drosophila nanos, regulate primordial germ cell development and survival in Caenorhabditis elegans. Development 126, 4861–4871 (1999)

  17. 17

    Jensen, K. B., Musunuru, K., Lewis, H. A., Burley, S. K. & Darnell, R. B. The tetranucleotide UCAY directs the specific recognition of RNA by the Nova K-homology 3 domain. Proc. Natl Acad. Sci. USA 97, 5740–5745 (2000)

  18. 18

    Brown, V. et al. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107, 477–487 (2001)

  19. 19

    Darnell, J. C. et al. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107, 489–499 (2001)

  20. 20

    Ostareck, D. H. et al. mRNA silencing in erythroid differentiation: hnRNP K and hnRNP E1 regulate 15-lipoxygenase translation from the 3′ end. Cell 89, 597–606 (1997)

  21. 21

    Wickens, M., Bernstein, D. S., Kimble, J. & Parker, R. A PUF family portrait: 3′UTR regulation as a way of life. Trends Genet. 18, 150–157 (2002)

  22. 22

    Saitoh, S. et al. Cid13 is a cytoplasmic poly(A) polymerase that regulates ribonucleotide reductase mRNA. Cell 109, 563–573 (2002)

  23. 23

    Wang, S. W., Toda, T., MacCallum, R., Harris, A. L. & Norbury, C. Cid1, a fission yeast protein required for S-M checkpoint control when DNA polymerase delta or epsilon is inactivated. Mol. Cell. Biol. 20, 3234–3244 (2000)

  24. 24

    Sambrook, J., Fritsch, E. F. & Maniatis, T. (ed.) Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989)

  25. 25

    Crittenden, S. L. & Kimble, J. in Cell: A Laboratory Manual (eds Spector, D., Goldman, R. & Leinwand, L.) 108.1–108.9 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1998)

  26. 26

    Lingner, J., Radtke, I., Wahle, E. & Keller, W. Purification and characterization of poly(A) polymerase from Saccharomyces cervisiae. J. Biol. Chem. 266, 8741–8746 (1991)

  27. 27

    Bateman, A. et al. The Pfam protein families database. Nucleic Acids Res. 30, 276–280 (2002)

  28. 28

    Thompson, J. D., Higgins, D. G. & Gibson, T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680 (1994)

  29. 29

    Gough, J., Karplus, K., Hughey, R. & Chothia, C. Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure. J. Mol. Biol. 313, 903–919 (2001)

  30. 30

    Felsenstein, J. PHYLIP (Phylogeny Inference Package) Version 3.5c (Department of Genetics, Univ. Washington, Seattle, 1993)

  31. 31

    Read, R. L., Martinho, R. G., Wang, S.-W., Carr, A. M. & Norbury, C. J. Cytoplasmic poly(A) polymerases mediate cellular responses to S phase arrest. Proc. Natl Acad. Sci. USA (in the press)

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We thank R. Read and C. Norbury for sharing unpublished observations, and S. Crittenden for comments on the manuscript. C.E. was supported by the Human Frontier Science Program, L.K. was supported by the American Cancer Society, J.K. is an investigator with the Howard Hughes Medical Institute, and M.W. is supported by the National Institutes of Health.

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Correspondence to Judith Kimble.

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Wang, L., Eckmann, C., Kadyk, L. et al. A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans. Nature 419, 312–316 (2002) doi:10.1038/nature01039

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