| Structural highlights
Function
[GLD2_CAEEL] Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail. Acts as a regulator of mitosis/meiosis required for progression through meiotic prophase during oogenesis and spermatogenesis and for promotion of the entry into meiosis from the mitotic cell cycle. May act by regulating and activating gld-1 mRNA activity in germline.[1] [2] [3] [4] [5] [6] [7] [GLD3_CAEEL] Required maternally for germline survival and embryogenesis. Forms a complex with gls-1 which promotes the oogenic cell fate by freeing the translational repressor fbf to repress sperm promoting factors. Promotes maturation of primary spermatocytes to mature sperm. Required during hermaphrodite development to promote sperm fate, which is critical for determining the normal number of sperm. Promotion of sperm fate is at the expense of oogenesis, possibly through the negative regulation of fbf. Required during male development for the continued production of sperm and inhibition of oogenesis. Together with gld-2, promotes the transition from mitosis to meiosis.[8] [9] [10]
Publication Abstract from PubMed
The Caenorhabditis elegans germ-line development defective (GLD)-2-GLD-3 complex up-regulates the expression of genes required for meiotic progression. GLD-2-GLD-3 acts by extending the short poly(A) tail of germ-line-specific mRNAs, switching them from a dormant state into a translationally active state. GLD-2 is a cytoplasmic noncanonical poly(A) polymerase that lacks the RNA-binding domain typical of the canonical nuclear poly(A)-polymerase Pap1. The activity of C. elegans GLD-2 in vivo and in vitro depends on its association with the multi-K homology (KH) domain-containing protein, GLD-3, a homolog of Bicaudal-C. We have identified a minimal polyadenylation complex that includes the conserved nucleotidyl-transferase core of GLD-2 and the N-terminal domain of GLD-3, and determined its structure at 2.3-A resolution. The structure shows that the N-terminal domain of GLD-3 does not fold into the predicted KH domain but wraps around the catalytic domain of GLD-2. The picture that emerges from the structural and biochemical data are that GLD-3 activates GLD-2 both indirectly by stabilizing the enzyme and directly by contributing positively charged residues near the RNA-binding cleft. The RNA-binding cleft of GLD-2 has distinct structural features compared with the poly(A)-polymerases Pap1 and Trf4. Consistently, GLD-2 has distinct biochemical properties: It displays unusual specificity in vitro for single-stranded RNAs with at least one adenosine at the 3' end. GLD-2 thus appears to have evolved specialized nucleotidyl-transferase properties that match the 3' end features of dormant cytoplasmic mRNAs.
Structural basis for the activation of the C. elegans noncanonical cytoplasmic poly(A)-polymerase GLD-2 by GLD-3.,Nakel K, Bonneau F, Eckmann CR, Conti E Proc Natl Acad Sci U S A. 2015 Jun 29. pii: 201504648. PMID:26124149[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang L, Eckmann CR, Kadyk LC, Wickens M, Kimble J. A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans. Nature. 2002 Sep 19;419(6904):312-6. PMID:12239571 doi:http://dx.doi.org/10.1038/nature01039
- ↑ Hansen D, Wilson-Berry L, Dang T, Schedl T. Control of the proliferation versus meiotic development decision in the C. elegans germline through regulation of GLD-1 protein accumulation. Development. 2004 Jan;131(1):93-104. Epub 2003 Dec 3. PMID:14660440 doi:http://dx.doi.org/10.1242/dev.00916
- ↑ Hansen D, Hubbard EJ, Schedl T. Multi-pathway control of the proliferation versus meiotic development decision in the Caenorhabditis elegans germline. Dev Biol. 2004 Apr 15;268(2):342-57. PMID:15063172 doi:http://dx.doi.org/10.1016/j.ydbio.2003.12.023
- ↑ Maine EM, Hansen D, Springer D, Vought VE. Caenorhabditis elegans atx-2 promotes germline proliferation and the oocyte fate. Genetics. 2004 Oct;168(2):817-30. PMID:15514056 doi:http://dx.doi.org/10.1534/genetics.104.029355
- ↑ Vought VE, Ohmachi M, Lee MH, Maine EM. EGO-1, a putative RNA-directed RNA polymerase, promotes germline proliferation in parallel with GLP-1/notch signaling and regulates the spatial organization of nuclear pore complexes and germline P granules in Caenorhabditis elegans. Genetics. 2005 Jul;170(3):1121-32. Epub 2005 May 23. PMID:15911573 doi:http://dx.doi.org/10.1534/genetics.105.042135
- ↑ Suh N, Jedamzik B, Eckmann CR, Wickens M, Kimble J. The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line. Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15108-12. Epub 2006 Sep 29. PMID:17012378 doi:http://dx.doi.org/10.1073/pnas.0607050103
- ↑ Kadyk LC, Kimble J. Genetic regulation of entry into meiosis in Caenorhabditis elegans. Development. 1998 May;125(10):1803-13. PMID:9550713
- ↑ Eckmann CR, Kraemer B, Wickens M, Kimble J. GLD-3, a bicaudal-C homolog that inhibits FBF to control germline sex determination in C. elegans. Dev Cell. 2002 Nov;3(5):697-710. PMID:12431376
- ↑ Eckmann CR, Crittenden SL, Suh N, Kimble J. GLD-3 and control of the mitosis/meiosis decision in the germline of Caenorhabditis elegans. Genetics. 2004 Sep;168(1):147-60. PMID:15454534 doi:10.1534/genetics.104.029264
- ↑ Rybarska A, Harterink M, Jedamzik B, Kupinski AP, Schmid M, Eckmann CR. GLS-1, a novel P granule component, modulates a network of conserved RNA regulators to influence germ cell fate decisions. PLoS Genet. 2009 May;5(5):e1000494. doi: 10.1371/journal.pgen.1000494. Epub 2009 , May 22. PMID:19461891 doi:10.1371/journal.pgen.1000494
- ↑ Nakel K, Bonneau F, Eckmann CR, Conti E. Structural basis for the activation of the C. elegans noncanonical cytoplasmic poly(A)-polymerase GLD-2 by GLD-3. Proc Natl Acad Sci U S A. 2015 Jun 29. pii: 201504648. PMID:26124149 doi:http://dx.doi.org/10.1073/pnas.1504648112
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