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A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans

Abstract

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.

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Acknowledgements

We thank R. Read and C. Norbury for sharing unpublished observations, and S. Crittenden for comments on the manuscript.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). https://doi.org/10.1038/nature01039

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