Translational Control in the Caenorhabditis elegans Germ Line

Part of the Advances in Experimental Medicine and Biology book series (volume 757)


Translational control is a prevalent form of gene expression regulation in the Caenorhabditis elegans germ line. Linking the amount of protein synthesis to mRNA quantity and translational accessibility in the cell cytoplasm provides unique advantages over DNA-based controls for developing germ cells. This mode of gene expression is especially exploited in germ cell fate decisions and during oogenesis, when the developing oocytes stockpile hundreds of different mRNAs required for early embryogenesis. Consequently, a dense web of RNA regulators, consisting of diverse RNA-binding proteins and RNA-modifying enzymes, control the translatability of entire mRNA expression programs. These RNA regulatory networks are tightly coupled to germ cell developmental progression and are themselves under translational control. The underlying molecular mechanisms and RNA codes embedded in the mRNA molecules are beginning to be understood. Hence, the C. elegans germ line offers fertile grounds for discovering post-transcriptional mRNA regulatory mechanisms and emerges as great model for a systems level understanding of translational control during development.


RNA regulatory network Post-transcriptional RNA regulation Translational control RNA-binding protein Polyadenylation Deadenylation RNA decay miRNA 


  1. Ahringer J, Kimble J (1991) Control of the sperm-oocyte switch in Caenorhabditis elegans hermaphrodites by the fem-3 3′ untranslated region. Nature 349(6307):346–348. doi:10.1038/349346a0 PubMedGoogle Scholar
  2. Amiri A, Keiper BD, Kawasaki I, Fan Y, Kohara Y, Rhoads RE, Strome S (2001) An isoform of eIF4E is a component of germ granules and is required for spermatogenesis in C. elegans. Development 128(20):3899–3912PubMedGoogle Scholar
  3. Ariz M, Mainpal R, Subramaniam K (2009) C. elegans RNA-binding proteins PUF-8 and MEX-3 function redundantly to promote germline stem cell mitosis. Dev Biol 326(2):295–304. doi:10.1016/j.ydbio.2008.11.024 PubMedGoogle Scholar
  4. Arur S, Ohmachi M, Nayak S, Hayes M, Miranda A, Hay A, Golden A, Schedl T (2009) Multiple ERK substrates execute single biological processes in Caenorhabditis elegans germ-line development. Proc Natl Acad Sci USA 106(12):4776–4781. doi:10.1073/pnas.0812285106 PubMedGoogle Scholar
  5. Arur S, Ohmachi M, Berkseth M, Nayak S, Hansen D, Zarkower D, Schedl T (2011) MPK-1 ERK controls membrane organization in C. elegans oogenesis via a sex-determination module. Dev Cell 20(5):677–688. doi:10.1016/j.devcel.2011.04.009 PubMedGoogle Scholar
  6. Audhya A, Hyndman F, McLeod IX, Maddox AS, Yates JR 3rd, Desai A, Oegema K (2005) A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans. J Cell Biol 171(2):267–279. doi:10.1083/jcb.200506124 PubMedGoogle Scholar
  7. Austin J, Kimble J (1987) glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell 51(4):589–599PubMedGoogle Scholar
  8. Bachorik JL, Kimble J (2005) Redundant control of the Caenorhabditis elegans sperm/oocyte switch by PUF-8 and FBF-1, two distinct PUF RNA-binding proteins. Proc Natl Acad Sci USA 102(31):10893–10897. doi:10.1073/pnas.0504593102 PubMedGoogle Scholar
  9. Baer BW, Kornberg RD (1980) Repeating structure of cytoplasmic poly(A)-ribonucleoprotein. Proc Natl Acad Sci USA 77(4):1890–1892PubMedGoogle Scholar
  10. Baer BW, Kornberg RD (1983) The protein responsible for the repeating structure of cytoplasmic poly(A)-ribonucleoprotein. J Cell Biol 96(3):717–721PubMedGoogle Scholar
  11. Barnard DC, Cao Q, Richter JD (2005) Differential phosphorylation controls Maskin association with eukaryotic translation initiation factor 4E and localization on the mitotic apparatus. Mol Cell Biol 25(17):7605–7615. doi:10.1128/MCB.25.17.7605-7615.2005 PubMedGoogle Scholar
  12. Barton MK, Kimble J (1990) fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans. Genetics 125(1):29–39PubMedGoogle Scholar
  13. Barton MK, Schedl TB, Kimble J (1987) Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans. Genetics 115(1):107–119PubMedGoogle Scholar
  14. Bernstein D, Hook B, Hajarnavis A, Opperman L, Wickens M (2005) Binding specificity and mRNA targets of a C. elegans PUF protein, FBF-1. RNA 11(4):447–458. doi:10.1261/rna.7255805
  15. Biedermann B, Wright J, Senften M, Kalchhauser I, Sarathy G, Lee MH, Ciosk R (2009) Translational repression of cyclin E prevents precocious mitosis and embryonic gene activation during C. elegans meiosis. Dev Cell 17(3):355–364. doi:10.1016/j.devcel.2009.08.003 PubMedGoogle Scholar
  16. Boag PR, Nakamura A, Blackwell TK (2005) A conserved RNA-protein complex component involved in physiological germline apoptosis regulation in C. elegans. Development 132(22):4975–4986. doi:10.1242/dev.02060 PubMedGoogle Scholar
  17. Boag PR, Atalay A, Robida S, Reinke V, Blackwell TK (2008) Protection of specific maternal messenger RNAs by the P body protein CGH-1 (Dhh1/RCK) during Caenorhabditis elegans oogenesis. J Cell Biol 182(3):543–557. doi:10.1083/jcb.200801183 PubMedGoogle Scholar
  18. Bourc’his D, Voinnet O (2010) A small-RNA perspective on gametogenesis, fertilization, and early zygotic development. Science 330(6004):617–622. doi:10.1126/science.1194776 PubMedGoogle Scholar
  19. Bowerman B, Kurz T (2006) Degrade to create: developmental requirements for ubiquitin-mediated proteolysis during early C. elegans embryogenesis. Development 133(5):773–784. doi:10.1242/dev.02276 PubMedGoogle Scholar
  20. Buchan JR, Yoon JH, Parker R (2011) Stress-specific composition, assembly and kinetics of stress granules in Saccharomyces cerevisiae. J Cell Sci 124(Pt 2):228–239. doi:10.1242/jcs.078444 PubMedGoogle Scholar
  21. Buchet-Poyau K, Courchet J, Le Hir H, Seraphin B, Scoazec JY, Duret L, Domon-Dell C, Freund JN, Billaud M (2007) Identification and characterization of human Mex-3 proteins, a novel family of evolutionarily conserved RNA-binding proteins differentially localized to processing bodies. Nucleic Acids Res 35(4):1289–1300. doi:10.1093/nar/gkm016 PubMedGoogle Scholar
  22. Ceron J, Rual JF, Chandra A, Dupuy D, Vidal M, van den Heuvel S (2007) Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity. BMC Dev Biol 7:30. doi:10.1186/1471-213X-7-30 PubMedGoogle Scholar
  23. Chen T, Damaj BB, Herrera C, Lasko P, Richard S (1997) Self-association of the single-KH-domain family members Sam68, GRP33, GLD-1, and Qk1: role of the KH domain. Mol Cell Biol 17(10):5707–5718PubMedGoogle Scholar
  24. Chu DS, Shakes DC (2012) Spermatogenesis. Advances in Experimental Medicine and Biology 757:171–203. (Chap. 7, this volume) Springer, New YorkGoogle Scholar
  25. Ciosk R, DePalma M, Priess JR (2004) ATX-2, the C. elegans ortholog of ataxin 2, functions in translational regulation in the germline. Development 131(19):4831–4841. doi:10.1242/dev.01352 PubMedGoogle Scholar
  26. Ciosk R, DePalma M, Priess JR (2006) Translational regulators maintain totipotency in the Caenorhabditis elegans germline. Science 311(5762):851–853. doi:10.1126/science.1122491 PubMedGoogle Scholar
  27. Clark-Maguire S, Mains PE (1994a) Localization of the mei-1 gene product of Caenorhaditis elegans, a meiotic-specific spindle component. J Cell Biol 126(1):199–209PubMedGoogle Scholar
  28. Clark-Maguire S, Mains PE (1994b) mei-1, a gene required for meiotic spindle formation in Caenorhabditis elegans, is a member of a family of ATPases. Genetics 136(2):533–546PubMedGoogle Scholar
  29. Clifford R, Lee MH, Nayak S, Ohmachi M, Giorgini F, Schedl T (2000) FOG-2, a novel F-box containing protein, associates with the GLD-1 RNA binding protein and directs male sex determination in the C. elegans hermaphrodite germline. Development 127(24):5265–5276PubMedGoogle Scholar
  30. Conine CC, Batista PJ, Gu W, Claycomb JM, Chaves DA, Shirayama M, Mello CC (2010) Argonautes ALG-3 and ALG-4 are required for spermatogenesis-specific 26 G-RNAs and thermotolerant sperm in Caenorhabditis elegans. Proc Natl Acad Sci USA 107(8):3588–3593. doi:10.1073/pnas.0911685107 PubMedGoogle Scholar
  31. Contreras V, Richardson MA, Hao E, Keiper BD (2008) Depletion of the cap-associated isoform of translation factor eIF4G induces germline apoptosis in C. elegans. Cell Death Differ 15(8):1232–1242. doi:10.1038/cdd.2008.46 PubMedGoogle Scholar
  32. Crittenden SL, Bernstein DS, Bachorik JL, Thompson BE, Gallegos M, Petcherski AG, Moulder G, Barstead R, Wickens M, Kimble J (2002) A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans. Nature 417(6889):660–663. doi:10.1038/nature754 PubMedGoogle Scholar
  33. Curtis D, Treiber DK, Tao F, Zamore PD, Williamson JR, Lehmann R (1997) A CCHC metal-binding domain in Nanos is essential for translational regulation. EMBO J 16(4):834–843. doi:10.1093/emboj/16.4.834 PubMedGoogle Scholar
  34. de Moor CH, Richter JD (1997) The Mos pathway regulates cytoplasmic polyadenylation in Xenopus oocytes. Mol Cell Biol 17(11):6419–6426PubMedGoogle Scholar
  35. DeBella LR, Hayashi A, Rose LS (2006) LET-711, the Caenorhabditis elegans NOT1 ortholog, is required for spindle positioning and regulation of microtubule length in embryos. Mol Biol Cell 17(11):4911–4924. doi:10.1091/mbc.E06-02-0107 PubMedGoogle Scholar
  36. Decker CJ, Parker R (1993) A turnover pathway for both stable and unstable mRNAs in yeast: evidence for a requirement for deadenylation. Genes Dev 7(8):1632–1643PubMedGoogle Scholar
  37. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (2004) Processing of primary microRNAs by the microprocessor complex. Nature 432(7014):231–235. doi:10.1038/nature03049 PubMedGoogle Scholar
  38. Detwiler MR, Reuben M, Li X, Rogers E, Lin R (2001) Two zinc finger proteins, OMA-1 and OMA-2, are redundantly required for oocyte maturation in C. elegans. Dev Cell 1(2):187–199PubMedGoogle Scholar
  39. Dinkova TD, Keiper BD, Korneeva NL, Aamodt EJ, Rhoads RE (2005) Translation of a small subset of Caenorhabditis elegans mRNAs is dependent on a specific eukaryotic translation initiation factor 4E isoform. Mol Cell Biol 25(1):100–113. doi:10.1128/MCB.25.1.100-113.2005 PubMedGoogle Scholar
  40. Draper BW, Mello CC, Bowerman B, Hardin J, Priess JR (1996) MEX-3 is a KH domain protein that regulates blastomere identity in early C. elegans embryos. Cell 87(2):205–216PubMedGoogle Scholar
  41. Eckmann CR, Kraemer B, Wickens M, Kimble J (2002) GLD-3, a bicaudal-C homolog that inhibits FBF to control germline sex determination in C. elegans. Dev Cell 3(5):697–710PubMedGoogle Scholar
  42. Eckmann CR, Crittenden SL, Suh N, Kimble J (2004) GLD-3 and control of the mitosis/meiosis decision in the germline of Caenorhabditis elegans. Genetics 168(1):147–160. doi:10.1534/genetics.104.029264 PubMedGoogle Scholar
  43. Eckmann CR, Rammelt C, Wahle E (2011) Control of poly(A) tail length. Wiley Interdiscip Rev RNA 2(3):348–361. doi:10.1002/wrna.56 PubMedGoogle Scholar
  44. Edwards TA, Pyle SE, Wharton RP, Aggarwal AK (2001) Structure of Pumilio reveals similarity between RNA and peptide binding motifs. Cell 105(2):281–289PubMedGoogle Scholar
  45. Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379. doi:10.1146/annurev-biochem-060308-103103 PubMedGoogle Scholar
  46. Francis R, Barton MK, Kimble J, Schedl T (1995a) gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans. Genetics 139(2):579–606PubMedGoogle Scholar
  47. Francis R, Maine E, Schedl T (1995b) Analysis of the multiple roles of gld-1 in germline development: interactions with the sex determination cascade and the glp-1 signaling pathway. Genetics 139(2):607–630PubMedGoogle Scholar
  48. Furuichi Y, LaFiandra A, Shatkin AJ (1977) 5′-Terminal structure and mRNA stability. Nature 266(5599):235–239PubMedGoogle Scholar
  49. Garneau NL, Wilusz J, Wilusz CJ (2007) The highways and byways of mRNA decay. Nat Rev Mol Cell Biol 8(2):113–126. doi:10.1038/nrm2104 PubMedGoogle Scholar
  50. Gebauer F, Hentze MW (2004) Molecular mechanisms of translational control. Nat Rev Mol Cell Biol 5(10):827–835. doi:10.1038/nrm1488 PubMedGoogle Scholar
  51. Goodwin EB, Okkema PG, Evans TC, Kimble J (1993) Translational regulation of tra-2 by its 3′ untranslated region controls sexual identity in C. elegans. Cell 75(2):329–339PubMedGoogle Scholar
  52. Goodwin EB, Hofstra K, Hurney CA, Mango S, Kimble J (1997) A genetic pathway for regulation of tra-2 translation. Development 124(3):749–758PubMedGoogle Scholar
  53. Graves LE, Segal S, Goodwin EB (1999) TRA-1 regulates the cellular distribution of the tra-2 mRNA in C. elegans. Nature 399(6738):802–805. doi:10.1038/21682 PubMedGoogle Scholar
  54. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, Baillie DL, Fire A, Ruvkun G, Mello CC (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106(1):23–34PubMedGoogle Scholar
  55. Guven-Ozkan T, Robertson SM, Nishi Y, Lin R (2010) zif-1 translational repression defines a second, mutually exclusive OMA function in germline transcriptional repression. Development 137(20):3373–3382. doi:10.1242/dev.055327 PubMedGoogle Scholar
  56. Hake LE, Mendez R, Richter JD (1998) Specificity of RNA binding by CPEB: requirement for RNA recognition motifs and a novel zinc finger. Mol Cell Biol 18(2):685–693PubMedGoogle Scholar
  57. Han T, Manoharan AP, Harkins TT, Bouffard P, Fitzpatrick C, Chu DS, Thierry-Mieg D, Thierry-Mieg J, Kim JK (2009) 26 G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans. Proc Natl Acad Sci USA 106(44):18674–18679. doi:10.1073/pnas.0906378106 PubMedGoogle Scholar
  58. Hanazawa M, Kawasaki I, Kunitomo H, Gengyo-Ando K, Bennett KL, Mitani S, Iino Y (2004) The Caenorhabditis elegans eukaryotic initiation factor 5A homologue, IFF-1, is required for germ cell proliferation, gametogenesis and localization of the P-granule component PGL-1. Mech Dev 121(3):213–224. doi:10.1016/j.mod.2004.02.001 PubMedGoogle Scholar
  59. Hansen D, Schedl T (2012) Stem cell proliferation versus meiotic fate decision in C. elegans. Advances in Experimental Medicine and Biology 757:71–99. (Chap. 4, this volume) Springer, New YorkGoogle Scholar
  60. Hansen D, Wilson-Berry L, Dang T, Schedl T (2004) Control of the proliferation versus meiotic development decision in the C. elegans germline through regulation of GLD-1 protein accumulation. Development 131(1):93–104. doi:10.1242/dev.00916 PubMedGoogle Scholar
  61. Hasegawa E, Karashima T, Sumiyoshi E, Yamamoto M (2006) C. elegans CPB-3 interacts with DAZ-1 and functions in multiple steps of germline development. Dev Biol 295(2):689–699. doi:10.1016/j.ydbio.2006.04.002 PubMedGoogle Scholar
  62. Henderson MA, Cronland E, Dunkelbarger S, Contreras V, Strome S, Keiper BD (2009) A germline-specific isoform of eIF4E (IFE-1) is required for efficient translation of stored mRNAs and maturation of both oocytes and sperm. J Cell Sci 122(Pt 10):1529–1539. doi:10.1242/jcs.046771 PubMedGoogle Scholar
  63. Hunter CP, Kenyon C (1996) Spatial and temporal controls target pal-1 blastomere-specification activity to a single blastomere lineage in C. elegans embryos. Cell 87(2):217–226PubMedGoogle Scholar
  64. Jackson RJ (2005) Alternative mechanisms of initiating translation of mammalian mRNAs. Biochem Soc Trans 33(Pt 6):1231–1241. doi:10.1042/BST20051231 PubMedGoogle Scholar
  65. Jadhav S, Rana M, Subramaniam K (2008) Multiple maternal proteins coordinate to restrict the translation of C. elegans nanos-2 to primordial germ cells. Development 135(10):1803–1812. doi:10.1242/dev.013656 PubMedGoogle Scholar
  66. Jan E, Yoon JW, Walterhouse D, Iannaccone P, Goodwin EB (1997) Conservation of the C. elegans tra-2 3′UTR translational control. EMBO J 16(20):6301–6313. doi:10.1093/emboj/16.20.6301 PubMedGoogle Scholar
  67. Jan E, Motzny CK, Graves LE, Goodwin EB (1999) The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans. EMBO J 18(1):258–269. doi:10.1093/emboj/18.1.258 PubMedGoogle Scholar
  68. Jankowska-Anyszka M, Lamphear BJ, Aamodt EJ, Harrington T, Darzynkiewicz E, Stolarski R, Rhoads RE (1998) Multiple isoforms of eukaryotic protein synthesis initiation factor 4E in Caenorhabditis elegans can distinguish between mono- and trimethylated mRNA cap structures. J Biol Chem 273(17):10538–10542PubMedGoogle Scholar
  69. Jones AR, Schedl T (1995) 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 9(12):1491–1504PubMedGoogle Scholar
  70. Jones AR, Francis R, Schedl T (1996) GLD-1, a cytoplasmic protein essential for oocyte differentiation, shows stage- and sex-specific expression during Caenorhabditis elegans germline development. Dev Biol 180(1):165–183. doi:10.1006/dbio.1996.0293 PubMedGoogle Scholar
  71. Jud MC, Czerwinski MJ, Wood MP, Young RA, Gallo CM, Bickel JS, Petty EL, Mason JM, Little BA, Padilla PA, Schisa JA (2008) Large P body-like RNPs form in C. elegans oocytes in response to arrested ovulation, heat shock, osmotic stress, and anoxia and are regulated by the major sperm protein pathway. Dev Biol 318(1):38–51. doi:10.1016/j.ydbio.2008.02.059 PubMedGoogle Scholar
  72. Kadyk LC, Kimble J (1998) Genetic regulation of entry into meiosis in Caenorhabditis elegans. Development 125(10):1803–1813PubMedGoogle Scholar
  73. Kadyk LC, Lambie EJ, Kimble J (1997) glp-3 is required for mitosis and meiosis in the Caenorhabditis elegans germ line. Genetics 145(1):111–121PubMedGoogle Scholar
  74. Kalchhauser I, Farley BM, Pauli S, Ryder SP, Ciosk R (2011) FBF represses the Cip/Kip cell-cycle inhibitor CKI-2 to promote self-renewal of germline stem cells in C. elegans. EMBO J. doi:10.1038/emboj.2011.263
  75. Kato M, de Lencastre A, Pincus Z, Slack FJ (2009) Dynamic expression of small non-coding RNAs, including novel microRNAs and piRNAs/21U-RNAs, during Caenorhabditis elegans development. Genome Biol 10(5):R54. doi:10.1186/gb-2009-10-5-r54 PubMedGoogle Scholar
  76. Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J, Fritzler MJ, Scheuner D, Kaufman RJ, Golan DE, Anderson P (2005) Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol 169(6):871–884. doi:10.1083/jcb.200502088 PubMedGoogle Scholar
  77. Keiper BD, Lamphear BJ, Deshpande AM, Jankowska-Anyszka M, Aamodt EJ, Blumenthal T, Rhoads RE (2000) Functional characterization of five eIF4E isoforms in Caenorhabditis elegans. J Biol Chem 275(14):10590–10596PubMedGoogle Scholar
  78. Kershner AM, Kimble J (2010) Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator. Proc Natl Acad Sci USA 107(8):3936–3941. doi:10.1073/pnas.1000495107 PubMedGoogle Scholar
  79. Kim KW, Nykamp K, Suh N, Bachorik JL, Wang L, Kimble J (2009a) Antagonism between GLD-2 binding partners controls gamete sex. Dev Cell 16(5):723–733. doi:10.1016/j.devcel.2009.04.002 PubMedGoogle Scholar
  80. Kim VN, Han J, Siomi MC (2009b) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10(2):126–139. doi:10.1038/nrm2632 PubMedGoogle Scholar
  81. Kim KW, Wilson TL, Kimble J (2010) GLD-2/RNP-8 cytoplasmic poly(A) polymerase is a broad-spectrum regulator of the oogenesis program. Proc Natl Acad Sci USA 107(40):17445–17450. doi:10.1073/pnas.1012611107 PubMedGoogle Scholar
  82. Kim S, Spike CA, Greenstein D (2012) Control of oocyte growth and meiotic maturation in C. elegans. Advances in Experimental Medicine and Biology 757:277–320. (Chap. 10, this volume) Springer, New YorkGoogle Scholar
  83. Klass M, Dow B, Herndon M (1982) Cell-specific transcriptional regulation of the major sperm protein in Caenorhabditis elegans. Dev Biol 93(1):152–164PubMedGoogle Scholar
  84. Knight SW, Bass BL (2001) A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 293(5538):2269–2271. doi:10.1126/science.1062039 PubMedGoogle Scholar
  85. Ko S, Park JH, Lee AR, Kim E, Jiyoung K, Kawasaki I, Shim YH (2010) Two mutations in pab-1 encoding poly(A)-binding protein show similar defects in germline stem cell proliferation but different longevity in C. elegans. Mol Cells 30(2):167–172. doi:10.1007/s10059-010-0103-2 PubMedGoogle Scholar
  86. Kraemer B, Crittenden S, Gallegos M, Moulder G, Barstead R, Kimble J, Wickens M (1999) NANOS-3 and FBF proteins physically interact to control the sperm-oocyte switch in Caenorhabditis elegans. Curr Biol 9(18):1009–1018PubMedGoogle Scholar
  87. Kuersten S, Goodwin EB (2003) The power of the 3′ UTR: translational control and development. Nat Rev Genet 4(8):626–637. doi:10.1038/nrg1125 PubMedGoogle Scholar
  88. Kuersten S, Segal SP, Verheyden J, LaMartina SM, Goodwin EB (2004) NXF-2, REF-1, and REF-2 affect the choice of nuclear export pathway for tra-2 mRNA in C. elegans. Mol Cell 14(5):599–610. doi:10.1016/j.molcel.2004.05.004 PubMedGoogle Scholar
  89. Lall S, Piano F, Davis RE (2005) Caenorhabditis elegans decapping proteins: localization and functional analysis of Dcp1, Dcp2, and DcpS during embryogenesis. Mol Biol Cell 16(12):5880–5890. doi:10.1091/mbc.E05-07-0622 PubMedGoogle Scholar
  90. Lamont LB, Crittenden SL, Bernstein D, Wickens M, Kimble J (2004) FBF-1 and FBF-2 regulate the size of the mitotic region in the C. elegans germline. Dev Cell 7(5):697–707. doi:10.1016/j.devcel.2004.09.013 PubMedGoogle Scholar
  91. Lasda EL, Blumenthal T (2011) Trans-splicing. Wiley Interdiscip Rev RNA 2(3):417–434. doi:10.1002/wrna.71 PubMedGoogle Scholar
  92. Lee MH, Schedl T (2001) Identification of in vivo mRNA targets of GLD-1, a maxi-KH motif containing protein required for C. elegans germ cell development. Genes Dev 15(18):2408–2420. doi:10.1101/gad.915901 Google Scholar
  93. Lee MH, Schedl T (2004) Translation repression by GLD-1 protects its mRNA targets from nonsense-mediated mRNA decay in C. elegans. Genes Dev 18(9):1047–1059. doi:10.1101/gad.1188404 Google Scholar
  94. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854PubMedGoogle Scholar
  95. Lee MH, Hook B, Lamont LB, Wickens M, Kimble J (2006) LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans. EMBO J 25(1):88–96. doi:10.1038/sj.emboj.7600901 PubMedGoogle Scholar
  96. Lee MH, Hook B, Pan G, Kershner AM, Merritt C, Seydoux G, Thomson JA, Wickens M, Kimble J (2007a) Conserved regulation of MAP kinase expression by PUF RNA-binding proteins. PLoS Genet 3(12):e233. doi:10.1371/journal.pgen.0030233 PubMedGoogle Scholar
  97. Lee MH, Ohmachi M, Arur S, Nayak S, Francis R, Church D, Lambie E, Schedl T (2007b) Multiple functions and dynamic activation of MPK-1 extracellular signal-regulated kinase signaling in Caenorhabditis elegans germline development. Genetics 177(4):2039–2062. doi:10.1534/genetics.107.081356 PubMedGoogle Scholar
  98. Li W, Boswell R, Wood WB (2000) mag-1, a homolog of Drosophila mago nashi, regulates hermaphrodite germ-line sex determination in Caenorhabditis elegans. Dev Biol 218(2):172–182. doi:10.1006/dbio.1999.9593 PubMedGoogle Scholar
  99. Li W, DeBella LR, Guven-Ozkan T, Lin R, Rose LS (2009) An eIF4E-binding protein regulates katanin protein levels in C. elegans embryos. J Cell Biol 187(1):33–42. doi:10.1083/jcb.200903003 PubMedGoogle Scholar
  100. Lu R, Yigit E, Li WX, Ding SW (2009) An RIG-I-Like RNA helicase mediates antiviral RNAi downstream of viral siRNA biogenesis in Caenorhabditis elegans. PLoS Pathog 5(2):e1000286. doi:10.1371/journal.ppat.1000286 PubMedGoogle Scholar
  101. Lublin AL, Evans TC (2007) The RNA-binding proteins PUF-5, PUF-6, and PUF-7 reveal multiple systems for maternal mRNA regulation during C. elegans oogenesis. Dev Biol 303(2):635–649. doi:10.1016/j.ydbio.2006.12.004 PubMedGoogle Scholar
  102. Lui DY, Colaiácovo MP (2012) Meiotic development in C. elegans. Advances in Experimental Medicine and Biology 757:133–170. (Chap. 6, this volume) Springer, New YorkGoogle Scholar
  103. Luitjens C, Gallegos M, Kraemer B, Kimble J, Wickens M (2000) CPEB proteins control two key steps in spermatogenesis in C. elegans. Genes Dev 14(20):2596–2609Google Scholar
  104. Maciejowski J, Ahn JH, Cipriani PG, Killian DJ, Chaudhary AL, Lee JI, Voutev R, Johnsen RC, Baillie DL, Gunsalus KC, Fitch DH, Hubbard EJ (2005) Autosomal genes of autosomal/X-linked duplicated gene pairs and germ-line proliferation in Caenorhabditis elegans. Genetics 169(4):1997–2011. doi:10.1534/genetics.104.040121 PubMedGoogle Scholar
  105. Mainpal R, Priti A, Subramaniam K (2011) PUF-8 suppresses the somatic transcription factor PAL-1 expression in C. elegans germline stem cells. Dev Biol 360(1):195–207. doi:10.1016/j.ydbio.2011.09.021 PubMedGoogle Scholar
  106. Marin VA, Evans TC (2003) Translational repression of a C. elegans Notch mRNA by the STAR/KH domain protein GLD-1. Development 130(12):2623–2632PubMedGoogle Scholar
  107. Maruyama R, Endo S, Sugimoto A, Yamamoto M (2005) Caenorhabditis elegans DAZ-1 is expressed in proliferating germ cells and directs proper nuclear organization and cytoplasmic core formation during oogenesis. Dev Biol 277(1):142–154. doi:10.1016/j.ydbio.2004.08.053 PubMedGoogle Scholar
  108. Mathews MB, Sonenberg N, Hershey J (2007) Translational control in biology and medicine. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  109. Mendez R, Richter JD (2001) Translational control by CPEB: a means to the end. Nat Rev Mol Cell Biol 2(7):521–529. doi:10.1038/35080081 PubMedGoogle Scholar
  110. Merritt C, Seydoux G (2010) The Puf RNA-binding proteins FBF-1 and FBF-2 inhibit the expression of synaptonemal complex proteins in germline stem cells. Development 137(11):1787–1798. doi:10.1242/dev.050799 PubMedGoogle Scholar
  111. Merritt C, Rasoloson D, Ko D, Seydoux G (2008) 3′ UTRs are the primary regulators of gene expression in the C. elegans germline. Curr Biol 18(19):1476–1482. doi:10.1016/j.cub.2008.08.013 PubMedGoogle Scholar
  112. Miyoshi H, Dwyer DS, Keiper BD, Jankowska-Anyszka M, Darzynkiewicz E, Rhoads RE (2002) Discrimination between mono- and trimethylated cap structures by two isoforms of Caenorhabditis elegans eIF4E. EMBO J 21(17):4680–4690PubMedGoogle Scholar
  113. Molin L, Puisieux A (2005) C. elegans homologue of the Caf1 gene, which encodes a subunit of the CCR4-NOT complex, is essential for embryonic and larval development and for meiotic progression. Gene 358:73–81. doi:10.1016/j.gene.2005.05.023 Google Scholar
  114. Mootz D, Ho DM, Hunter CP (2004) The STAR/Maxi-KH domain protein GLD-1 mediates a developmental switch in the translational control of C. elegans PAL-1. Development 131(14):3263–3272. doi:10.1242/dev.01196 PubMedGoogle Scholar
  115. Munroe D, Jacobson A (1990) mRNA poly(A) tail, a 3′ enhancer of translational initiation. Mol Cell Biol 10(7):3441–3455PubMedGoogle Scholar
  116. Nakamura M, Ando R, Nakazawa T, Yudazono T, Tsutsumi N, Hatanaka N, Ohgake T, Hanaoka F, Eki T (2007) Dicer-related drh-3 gene functions in germ-line development by maintenance of chromosomal integrity in Caenorhabditis elegans. Genes Cells 12(9):997–1010. doi:10.1111/j.1365-2443.2007.01111.x PubMedGoogle Scholar
  117. Nakel K, Hartung SA, Bonneau F, Eckmann CR, Conti E (2010) Four KH domains of the C. elegans Bicaudal-C ortholog GLD-3 form a globular structural platform. RNA 16(11):2058–2067. doi:10.1261/rna.2315010 Google Scholar
  118. Nelson MR, Leidal AM, Smibert CA (2004) Drosophila Cup is an eIF4E-binding protein that functions in Smaug-mediated translational repression. EMBO J 23(1):150–159. doi:10.1038/sj.emboj.7600026 PubMedGoogle Scholar
  119. Nolde MJ, Saka N, Reinert KL, Slack FJ (2007) The Caenorhabditis elegans pumilio homolog, puf-9, is required for the 3′UTR-mediated repression of the let-7 microRNA target gene, hbl-1. Dev Biol 305(2):551–563. doi:10.1016/j.ydbio.2007.02.040 PubMedGoogle Scholar
  120. Nykamp K, Lee MH, Kimble J (2008) C. elegans La-related protein, LARP-1, localizes to ­germline P bodies and attenuates Ras-MAPK signaling during oogenesis. RNA 14(7):1378–1389. doi:10.1261/rna.1066008 Google Scholar
  121. Ogura K, Kishimoto N, Mitani S, Gengyo-Ando K, Kohara Y (2003) Translational control of maternal glp-1 mRNA by POS-1 and its interacting protein SPN-4 in Caenorhabditis elegans. Development 130(11):2495–2503PubMedGoogle Scholar
  122. Opperman L, Hook B, DeFino M, Bernstein DS, Wickens M (2005) A single spacer nucleotide determines the specificities of two mRNA regulatory proteins. Nat Struct Mol Biol 12(11):945–951. doi:10.1038/nsmb1010 PubMedGoogle Scholar
  123. Otero LJ, Ashe MP, Sachs AB (1999) The yeast poly(A)-binding protein Pab1p stimulates in vitro poly(A)-dependent and cap-dependent translation by distinct mechanisms. EMBO J 18(11):3153–3163. doi:10.1093/emboj/18.11.3153 PubMedGoogle Scholar
  124. Pagano JM, Farley BM, Essien KI, Ryder SP (2009) RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX-3. Proc Natl Acad Sci USA 106(48):20252–20257. doi:10.1073/pnas.0907916106 PubMedGoogle Scholar
  125. Priess JR, Schnabel H, Schnabel R (1987) The glp-1 locus and cellular interactions in early C. elegans embryos. Cell 51(4):601–611PubMedGoogle Scholar
  126. Reddy R, Singh R, Shimba S (1992) Methylated cap structures in eukaryotic RNAs: structure, synthesis and functions. Pharmacol Ther 54(3):249–267PubMedGoogle Scholar
  127. Rhoads RE (2009) eIF4E: new family members, new binding partners, new roles. J Biol Chem 284(25):16711–16715. doi:10.1074/jbc.R900002200 PubMedGoogle Scholar
  128. Richter JD (2007) CPEB: a life in translation. Trends Biochem Sci 32(6):279–285. doi:10.1016/j.tibs.2007.04.004 PubMedGoogle Scholar
  129. Robertson S, Lin R (2012) The oocyte-to-embryo transition. Advances in Experimental Medicine and Biology, 757:351–372. (Chap. 12, this volume) Springer, New YorkGoogle Scholar
  130. Rybarska A, Harterink M, Jedamzik B, Kupinski AP, Schmid M, Eckmann CR (2009) GLS-1, a novel P granule component, modulates a network of conserved RNA regulators to influence germ cell fate decisions. PLoS Genet 5(5):e1000494. doi:10.1371/journal.pgen.1000494 PubMedGoogle Scholar
  131. Ryder SP, Frater LA, Abramovitz DL, Goodwin EB, Williamson JR (2004) RNA target specificity of the STAR/GSG domain post-transcriptional regulatory protein GLD-1. Nat Struct Mol Biol 11(1):20–28. doi:10.1038/nsmb706 PubMedGoogle Scholar
  132. Sachs A, Wahle E (1993) Poly(A) tail metabolism and function in eucaryotes. J Biol Chem 268(31):22955–22958PubMedGoogle Scholar
  133. Sachs AB, Bond MW, Kornberg RD (1986) A single gene from yeast for both nuclear and cytoplasmic polyadenylate-binding proteins: domain structure and expression. Cell 45(6):827–835PubMedGoogle Scholar
  134. Sachs AB, Davis RW, Kornberg RD (1987) A single domain of yeast poly(A)-binding protein is necessary and sufficient for RNA binding and cell viability. Mol Cell Biol 7(9):3268–3276PubMedGoogle Scholar
  135. Schisa JA, Pitt JN, Priess JR (2001) Analysis of RNA associated with P granules in germ cells of C. elegans adults. Development 128(8):1287–1298PubMedGoogle Scholar
  136. Schmid M, Kuchler B, Eckmann CR (2009) Two conserved regulatory cytoplasmic poly(A) polymerases, GLD-4 and GLD-2, regulate meiotic progression in C. elegans. Genes Dev 23(7):824–836. doi:10.1101/gad.494009 Google Scholar
  137. Schumacher B, Hanazawa M, Lee MH, Nayak S, Volkmann K, Hofmann ER, Hengartner M, Schedl T, Gartner A (2005) Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. Cell 120(3):357–368. doi:10.1016/j.cell.2004.12.009 Google Scholar
  138. Segal SP, Graves LE, Verheyden J, Goodwin EB (2001) RNA-regulated TRA-1 nuclear export controls sexual fate. Dev Cell 1(4):539–551PubMedGoogle Scholar
  139. Seydoux G, Fire A (1994) Soma-germline asymmetry in the distributions of embryonic RNAs in Caenorhabditis elegans. Development 120(10):2823–2834PubMedGoogle Scholar
  140. She X, Xu X, Fedotov A, Kelly WG, Maine EM (2009) Regulation of heterochromatin assembly on unpaired chromosomes during Caenorhabditis elegans meiosis by components of a small RNA-mediated pathway. PLoS Genet 5(8):e1000624. doi:10.1371/journal.pgen.1000624 PubMedGoogle Scholar
  141. Sheth U, Pitt J, Dennis S, Priess JR (2010) Perinuclear P granules are the principal sites of mRNA export in adult C. elegans germ cells. Development 137(8):1305–1314. doi:10.1242/dev.044255 PubMedGoogle Scholar
  142. Shimotohno K, Kodama Y, Hashimoto J, Miura KI (1977) Importance of 5′-terminal blocking structure to stabilize mRNA in eukaryotic protein synthesis. Proc Natl Acad Sci USA 74(7):2734–2738PubMedGoogle Scholar
  143. Simmer F, Moorman C, van der Linden AM, Kuijk E, van den Berghe PV, Kamath RS, Fraser AG, Ahringer J, Plasterk RH (2003) Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol 1(1):E12. doi:10.1371/journal.pbio.0000012 PubMedGoogle Scholar
  144. Song A, Labella S, Korneeva NL, Keiper BD, Aamodt EJ, Zetka M, Rhoads RE (2010) A C. elegans eIF4E-family member upregulates translation at elevated temperatures of mRNAs encoding MSH-5 and other meiotic crossover proteins. J Cell Sci 123(Pt 13):2228–2237. doi:10.1242/jcs.063107 Google Scholar
  145. Sonnichsen B, Koski LB, Walsh A, Marschall P, Neumann B, Brehm M, Alleaume AM, Artelt J, Bettencourt P, Cassin E, Hewitson M, Holz C, Khan M, Lazik S, Martin C, Nitzsche B, Ruer M, Stamford J, Winzi M, Heinkel R, Roder M, Finell J, Hantsch H, Jones SJ, Jones M, Piano F, Gunsalus KC, Oegema K, Gonczy P, Coulson A, Hyman AA, Echeverri CJ (2005) Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434(7032):462–469. doi:10.1038/nature03353 PubMedGoogle Scholar
  146. Squirrell JM, Eggers ZT, Luedke N, Saari B, Grimson A, Lyons GE, Anderson P, White JG (2006) CAR-1, a protein that localizes with the mRNA decapping component DCAP-1, is required for cytokinesis and ER organization in Caenorhabditis elegans embryos. Mol Biol Cell 17(1):336–344. doi:10.1091/mbc.E05-09-0874 PubMedGoogle Scholar
  147. Srayko M, Buster DW, Bazirgan OA, McNally FJ, Mains PE (2000) MEI-1/MEI-2 katanin-like microtubule severing activity is required for Caenorhabditis elegans meiosis. Genes Dev 14(9):1072–1084PubMedGoogle Scholar
  148. Starck J (1977) Autoradiographic study of RNA-synthesis in Caenorhabditis-elegans (Bergerac Variety) oogenesis. Biol Cellulaire 30(2):181Google Scholar
  149. Starck J, Gibert MA, Brun J, Bosch C (1983) Ribosomal-RNA synthesis and processing during oogenesis of the free living nematode Caenorhabditis-elegans. Comp Biochem Phys B 75(4):575–580Google Scholar
  150. Stebbins-Boaz B, Hake LE, Richter JD (1996) CPEB controls the cytoplasmic polyadenylation of cyclin, Cdk2 and c-mos mRNAs and is necessary for oocyte maturation in Xenopus. EMBO J 15(10):2582–2592PubMedGoogle Scholar
  151. Stebbins-Boaz B, Cao Q, de Moor CH, Mendez R, Richter JD (1999) Maskin is a CPEB-associated factor that transiently interacts with elF-4E. Mol Cell 4(6):1017–1027PubMedGoogle Scholar
  152. Strome S (2005) Specification of the germ line. WormBook:1–10. doi:10.1895/wormbook.1.9.1
  153. Stumpf CR, Kimble J, Wickens M (2008) A Caenorhabditis elegans PUF protein family with distinct RNA binding specificity. RNA 14(8):1550–1557. doi:10.1261/rna.1095908 PubMedGoogle Scholar
  154. Subramaniam K, Seydoux G (2003) Dedifferentiation of primary spermatocytes into germ cell tumors in C. elegans lacking the pumilio-like protein PUF-8. Curr Biol 13(2):134–139PubMedGoogle Scholar
  155. Suh N, Jedamzik B, Eckmann CR, Wickens M, Kimble J (2006) The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line. Proc Natl Acad Sci USA 103(41):15108–15112. doi:10.1073/pnas.0607050103 PubMedGoogle Scholar
  156. Suh N, Crittenden SL, Goldstrohm A, Hook B, Thompson B, Wickens M, Kimble J (2009) FBF and its dual control of gld-1 expression in the Caenorhabditis elegans germline. Genetics 181(4):1249–1260. doi:10.1534/genetics.108.099440 PubMedGoogle Scholar
  157. Tabara H, Yigit E, Siomi H, Mello CC (2002) The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans. Cell 109(7):861–871PubMedGoogle Scholar
  158. Tarun SZ Jr, Sachs AB (1995) A common function for mRNA 5′ and 3′ ends in translation initiation in yeast. Genes Dev 9(23):2997–3007PubMedGoogle Scholar
  159. Thompson SR, Goodwin EB, Wickens M (2000) Rapid deadenylation and Poly(A)-dependent translational repression mediated by the Caenorhabditis elegans tra-2 3′ untranslated region in Xenopus embryos. Mol Cell Biol 20(6):2129–2137PubMedGoogle Scholar
  160. Thompson BE, Bernstein DS, Bachorik JL, Petcherski AG, Wickens M, Kimble J (2005) Dose-dependent control of proliferation and sperm specification by FOG-1/CPEB. Development 132(15):3471–3481. doi:10.1242/dev.01921 PubMedGoogle Scholar
  161. Tursun B, Patel T, Kratsios P, Hobert O (2011) Direct conversion of C. elegans germ cells into specific neuron types. Science 331(6015):304–308. doi:10.1126/science.1199082 Google Scholar
  162. Valverde R, Edwards L, Regan L (2008) Structure and function of KH domains. FEBS J 275(11):2712–2726. doi:10.1111/j.1742-4658.2008.06411.x PubMedGoogle Scholar
  163. Vernet C, Artzt K (1997) STAR, a gene family involved in signal transduction and activation of RNA. Trends Genet 13(12):479–484PubMedGoogle Scholar
  164. Wang JT, Seydoux S (2012) Germ cell specification. Advances in Experimental Medicine and Biology 757:17– 39. (Chap. 2, this volume) Springer, New YorkGoogle Scholar
  165. Wang L, Eckmann CR, Kadyk LC, Wickens M, Kimble J (2002) A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans. Nature 419(6904):312–316. doi:10.1038/nature01039 PubMedGoogle Scholar
  166. Wang X, Zhao Y, Wong K, Ehlers P, Kohara Y, Jones SJ, Marra MA, Holt RA, Moerman DG, Hansen D (2009a) Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE. BMC Genomics 10:213. doi:10.1186/1471-2164-10-213 PubMedGoogle Scholar
  167. Wang Y, Opperman L, Wickens M, Hall TM (2009b) Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein. Proc Natl Acad Sci USA 106(48):20186–20191. doi:10.1073/pnas.0812076106 PubMedGoogle Scholar
  168. Wells SE, Hillner PE, Vale RD, Sachs AB (1998) Circularization of mRNA by eukaryotic translation initiation factors. Mol Cell 2(1):135–140PubMedGoogle Scholar
  169. Wickens M, Bernstein DS, Kimble J, Parker R (2002) A PUF family portrait: 3′UTR regulation as a way of life. Trends Genet 18(3):150–157PubMedGoogle Scholar
  170. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862PubMedGoogle Scholar
  171. Wilkie GS, Dickson KS, Gray NK (2003) Regulation of mRNA translation by 5′- and 3′-UTR-binding factors. Trends Biochem Sci 28(4):182–188PubMedGoogle Scholar
  172. Wright JE, Gaidatzis D, Senften M, Farley BM, Westhof E, Ryder SP, Ciosk R (2011) A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1. EMBO J 30(3):533–545. doi:10.1038/emboj.2010.334 PubMedGoogle Scholar
  173. Yu X, Vought VE, Conradt B, Maine EM (2006) Eukaryotic translation initiation factor 5B activity regulates larval growth rate and germline development in Caenorhabditis elegans. Genesis 44(9):412–418. doi:10.1002/dvg.20232 PubMedGoogle Scholar
  174. Zanetti S, Puoti A (2012) Sex determination in the C. elegans germline. Advances in Experimental Medicine and Biology 757:41–69. (Chap. 3, this volume) Springer, New YorkGoogle Scholar
  175. Zanin E, Pacquelet A, Scheckel C, Ciosk R, Gotta M (2010) LARP-1 promotes oogenesis by repressing fem-3 in the C. elegans germline. J Cell Sci 123(Pt 16):2717–2724. doi:10.1242/jcs.066761 Google Scholar
  176. Zhang B, Gallegos M, Puoti A, Durkin E, Fields S, Kimble J, Wickens MP (1997) A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature 390(6659):477–484. doi:10.1038/37297 PubMedGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Max Planck Institute of Molecular Cell Biology and GeneticsDresdenGermany

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