Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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)

    Google Scholar 

  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)

    Google Scholar 

  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)

    CAS  PubMed  Google Scholar 

  4. 4

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

    CAS  PubMed  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  9. 9

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

    ADS  CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

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

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  PubMed  Google Scholar 

  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)

    ADS  CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  22. 22

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

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    Google Scholar 

  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)

    CAS  PubMed  Google Scholar 

  27. 27

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

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  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)

    CAS  Article  Google Scholar 

  30. 30

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

    Google Scholar 

  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)

Download references


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.

Author information



Corresponding author

Correspondence to Judith Kimble.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing