Tudor protein is expressed throughout the life cycle, beginning in the early stages of germ-line development in the female. During oogenesis, tud mRNA appears to be present in the oocyte precursor within the germarial cysts, and in stages 1-3 it accumulates within the developing oocyte. The transcript is localized to the posterior half of the oocyte during oogenetic stages 4-7 but is not detectable within the ooplasm by egg deposition and throughout early embryogenesis (Golumbeski, 1991).

Mutations in the tudor locus of Drosophila affect two distinct determinative processes in embryogenesis; segmentation of the abdomen and determination of the primordial germ cells. The distribution of Tudor protein during embryogenesis, and the effect of various mutations on its distribution, suggest that Tudor may carry out these functions separately, based on its location in the embryo. The protein is concentrated in the posterior pole cytoplasm (germ plasm), where it is found in polar granules and mitochondria. Throughout the rest of the embryo, Tudor is associated with the cleavage nuclei. Mutations in all maternal genes known to be required for the normal functioning of the germ plasm eliminate the posterior localization of Tudor, whereas mutations in genes required for the functioning of the abdominal determinant disrupt the localization around nuclei. Analysis of embryos of different maternal genotypes indicates that the average number of pole cells formed is correlated with the amount of Tudor protein that accumulates in the germ plasm. These results suggest that Tudor localized in the germ plasm is instrumental in germ cell determination, whereas nuclear-associated Tudor protein is involved in determination of segmental pattern in the abdomen (Bardsley, 1993).

Effects of Mutation or Deletion

Developmental analysis of a newly isolated maternal effect grandchildless mutant, tudor, in Drosophila indicates that tud+ activity is required during oogenesis for the determination and/or formation of primordial germ cells (pole cells) and for normal embryonic abdominal segmentation. Regardless of their genotype, progeny of females homozygous for strong alleles (tud1 and tud3) never form pole cells, apparently lack polar granules in the germ plasm, and approximately 40% of them die during late embryogenesis exhibiting severe abdominal segmentation pattern defects. Females carrying weak allele, tud4, produce progeny with some functional pole cells and form polar granules approximately one-third the size of those observed in wild-type oocytes and embryos. No segmentation abnormalities are observed in the inviable embryos derived from tud4/tud4 females (Boswell, 1985).

Pole cells and posterior segmentation in Drosophila are specified by maternally encoded genes whose products accumulate at the posterior pole of the oocyte. Among these genes is tudor. Progeny of hypomorphic tud mothers lack pole cells and have variable posterior patterning defects. A null allele was isolated to further investigate tud function. While no pole cells are ever observed in embryos from tud-null mothers, 15% of these embryos have normal posterior patterning. Oskar (Osk) and Vasa (Vas) proteins, and nanos (nos) RNA, all initially localize to the pole plasm of tud-null oocytes and embryos from tud-null mothers, while localization of germ cell-less (gcl) and polar granule component (pgc), is undetectable or severely reduced. In embryos from tud-null mothers, polar granules are greatly reduced in number, size, and electron density. Thus, tud is dispensable for somatic patterning, but essential for pole cell specification and polar granule formation (Thomson, 2004).

Tudor protein is essential for the localization of mitochondrial RNAs in polar granules of Drosophila embryos

In Drosophila, polar plasm contains polar granules, which deposit the factors required for the formation of pole cells, germ line progenitors. Polar granules are tightly associated with mitochondria in early embryos, suggesting that mitochondria could contribute to pole cell formation. Mitochondrial large and small rRNAs (mtrRNAs) are transported from mitochondria to polar granules prior to pole cell formation and the large rRNA is essential for pole cell formation. The localization of mtrRNAs is diminished in embryos laid by tudor mutant females, although the polar granules are maintained. It was also found that Tud protein colocalizes with mtrRNAs at the boundaries between mitochondria and polar granules when the transport of mtrRNAs takes place. These observations suggest that Tud mediates the transport of mtrRNAs from mitochondria to polar granules (Amikura, 2001).

Mitochondria are organelles originated from a eubacterial symbiont and now functionally integrated into the eukaryotic cells. While the primary roles of the mitochondria are oxidative phosphorylation and biosynthesis of many metabolites, it has now become evident that they are also involved in the cellular events that play critical roles in development. One remarkable example is their involvement in germ line formation. In Drosophila, formation of the germ line progenitors, or pole cells, is induced by polar plasm localized in the posterior pole region of egg cytoplasm. The polar plasm contains mitochondria and polar granules which have been regarded as the structures essential for pole cell formation. Earlier ultrastructural studies have shown that both organelles become associated with each other at stages prior to pole cell formation, suggesting that mitochondria contribute to pole cell formation (Amikura, 2001).

Mitochondrial large rRNA (mtlrRNA) and small rRNA (mtsrRNA) are both transported from mitochondria and are localized on the surface of polar granules (hereafter we refer to the rRNAs outside mitochondria as extra-mitochondrial rRNAs). Injection of mtlrRNA restores pole-cell-forming ability to UV-irradiated embryos, and reduction of the extra-mitochondrial mtlrRNA results in the failure to form pole cells. These observations indicate that the extra-mitochondrial mtlrRNA on polar granules has an essential role in pole cell formation, presumably cooperating with mtsrRNA. Thus, the transport of mtrRNAs from mitochondria to polar granules is a critical step for pole cell formation. However, the molecule(s) mediating this transport remains elusive (Amikura, 2001).

It has been reported that the localization of the extra-mitochondrial mtrRNAs at the posterior pole region of embryos was impaired by mutation of any one of the maternally acting genes, namely oskar (osk), vasa (vas) and tudor (tud). These genes have been identified as the ones required for pole cell formation as well as for polar granule assembly. These genes all produce proteins localized to polar granules, and the association of these proteins with polar granules occurs stepwise and in a hierarchical manner: each subsequent localization depends on the activity of the preceding genes. The most downstream gene, tud, encodes a protein localized in mitochondria as well as in polar granules. This observation led to the idea that Tud may mediate the transport of mtrRNAs from mitochondria to polar granules (Amikura, 2001).

However, the possibility remained that the delocalization of extra-mitochondrial mtrRNAs from the posterior of tud mutant embryos is merely caused by their incapability to form polar granules, which tether the RNAs to the posterior. To exclude this possibility the effects of tud mutations on polar granules and mtrRNAs distribution were analyzed at a light and an electron microscopic level. In early embryos derived from tud mutant females, a polar granule component, Vas protein was normally localized in polar plasm, while extra-mitochondrial mtrRNAs were undetectable in the cytoplasm. Compatible with this observation, tud mutant embryos contained polar granules, although their number and size were decreased. These polar granules were associated with mitochondria during the early cleavage stage. However, no mtrRNA signal was observed in the polar granules. In normal embryos, Tud and mtrRNAs colocalized at the boundaries between mitochondria and polar granules, when the transport of mtrRNAs takes place. These ultrastructural data strongly support the idea that Tud mediates the transport of mtrRNAs from mitochondria to polar granules (Amikura, 2001).

Reference names in red indicate recommended papers.

Search PubMed for articles about Drosophila Tudor

Amikura, R., Hanyu, K., Kashikawa, M. and Kobayashi, S. (2001). Tudor protein is essential for the localization of mitochondrial RNAs in polar granules of Drosophila embryos. Mech. Dev. 107: 97-104. Medline abstract: 11520666

Ancelin, K., Lange, U. C., Hajkova, P., Schneider, R., Bannister, A. J., Kouzarides, T. and Surani, M. A. (2006). Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat. Cell Biol. 8: 623-630. Medline abstract: 16699504

Anne, J. and Mechler, B. M. (2005). Valois, a component of the nuage and pole plasm, is involved in assembly of these structures, and binds to Tudor and the methyltransferase Capsuleen. Development 132(9): 2167-77. 15800004

Anne, J. et al. (2007). Arginine methyltransferase Capsuléen is essential for methylation of spliceosomal Sm proteins and germ cell formation in Drosophila. Development 134: 137-146. Medline abstract: 17164419

Arkov, A. L., Wang, J.-Y. S., Ramos, A. and Lehmann, R. (2006). The role of Tudor domains in germline development and polar granule architecture. Development 133: 4053-4062. Medline abstract: 16971472

Bardsley, A., McDonald, K. and Boswell, R. E. (1993). Distribution of Tudor protein in the Drosophila embryo suggests separation of functions based on site of localization. Development 119: 207-219. 8275857

Boswell, R. E. and Mahowald, A. P. (1985). tudor, a gene required for assembly of the germ plasm in Drosophila melanogaster. Cell 43: 97-104. Medline abstract: 3935320

Brahms, H., Meheus, L., de Brabandere, V., Fischer, U. and L¸hrmann, R. (2001). Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein. RNA 7: 1531-1542. Medline abstract: 11720283

Bühler, D., Raker, V., Lührmann, R. and Fischer, U. (1999). Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: implications for spinal muscular atrophy. Hum. Mol. Genet. 8: 2351-2357. Medline abstract: 10556282

Cavey, M., Hijal, S., Zhang, X. and Suter, B. (2005). Drosophila valois encodes a divergent WD protein that is required for Vasa localization and Oskar protein accumulation. Development 132(3): 459-68. 15634703

Charier, G., Couprie, J., Alpha-Bazin, B., Meyer, V., Quéméneur, E., GuČrois, R., Callebaut, I., Gilquin, B. and Zinn-Justin, S. (2004). The Tudor tandem of 53BP1: a new structural motif involved in DNA and RG-rich peptide binding. Structure 12: 1551-1562. Medline abstract: 15341721

Cheng, D., Cote, J., Shaaban, S. and Bedford, M. T. (2007). The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing. Mol. Cell 25(1): 71-83. Medline abstract: 17218272

Côté, J. and Richard, S. (2005). Tudor domains bind symmetrical dimethylated arginines. J. Biol. Chem. 280: 28476-28483. Medline abstract: 15955813

Chuma, S., et al. (2003). Mouse Tudor Repeat-1 (MTR-1) is a novel component of chromatoid bodies/nuages in male germ cells and forms a complex with snRNPs. Mech. Dev. 120(9): 979-90. Medline abstract: 14550528

Chuma, S., et al. (2006). Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice. Proc. Natl. Acad. Sci. 103(43): 15894-9. Medline abstract: 17038506

Ephrussi, A. and Lehmann, R. (1992). Induction of germ cell formation by oskar. Nature 358: 387-392. Medline abstract: 1641021

Gavis, E. R. and Lehmann, R. (1994). Translational regulation of nanos by RNA localization. Nature 369: 315-318. Medline abstract: 7514276

Golumbeski, G. S., Bardsley, A., Tax, F. and Boswell, R. E. (1991). tudor, a posterior-group gene of Drosophila melanogaster, encodes a novel protein and an mRNA localized during mid-oogenesis. Genes Dev. 5: 2060-2070. Medline abstract: 1936993

Gonsalvez, G. B., Rajendra, T. K., Tian, L. and Matera, A. G. (2006). The Sm-protein methyl transferase, dart5, is essential for germ-cell specification and maintenance. Curr. Biol. 16: 1077-1089. Medline abstract: 16753561

Hay, B., Jan, L. Y. and Jan, Y. N. (1990). Localization of vasa, a component of Drosophila polar granules, in maternal-effect mutants that alter embryonic anteroposterior polarity. Development 109: 425-33

Hosokawa, M., et al. (2007). Tudor-related proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: domain composition, intracellular localization, and function in male germ cells in mice. Dev. Biol. 301(1): 38-52. Medline abstract: 17141210

Huang, Y., Fang, J., Bedford, M. T., Zhang, Y. and Xu, R. M. (2006). Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A. Science 312:748-751. Medline abstract: 16601153

Huyen, Y., Zgheib, O., Ditullio, R. A., Jr, Gorgoulis, V. G., Zacharatos, P., Petty, T. J., Sheston, E. A., Mellert, H. S., Stavridi, E. S. and Halazonetis, T. D. (2004). Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432: 406-411. Medline abstract: 15525939

Kim, J., Daniel, J., Espejo, A., Lake, A., Krishna, M., Xia, L., Zhang, Y. and Bedford, M. T. (2006). Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO Rep. 7: 397-403. Medline abstract:

Kotani, T., et al. (2007). A novel mutation at the N-terminal of SMN Tudor domain inhibits its interaction with target proteins. J. Neurol. 254(5): 624-30. Medline abstract: 17415510

Lasko, P. F. and Ashburner, M. (1990). Posterior localization of vasa protein correlates with, but is not sufficient for, pole cell development. Genes Dev. 4(6): 905-21. PubMed citation: 2384213

Maurer-Stroh, S., Dickens, N. J., Hughes-Davies, L., Kouzarides, T., Eisenhaber, F. and Ponting, C. P. (2003). The Tudor domain 'Royal Family': Tudor, plant Agenet, Chromo, PWWP and MBT domains. Trends Biochem. Sci. 28: 69-74. Medline abstract: 12575993

Nakamura, A., Amikura, R., Mukai, M., Kobayashi, S. and Lasko, P. F. (1996). Requirement for a noncoding RNA in Drosophila polar granules for germ cell establishment. Science 274: 2075-2079. Medline abstract: 8953037

Olesnicky, E. C. and Desplan, C. (2007). Distinct mechanisms for mRNA localization during embryonic axis specification in the wasp Nasonia. Dev. Biol. 306(1): 134-42. PubMed citation: 17434472

Ponting, C. P. (1997). Tudor domains in proteins that interact with RNA. Trends Biochem. Sci. 22: 51-52. 9048482

Ramos, A., Hollingworth, D., Adinolfi, S., Castets, M., Kelly, G., Frenkiel, T. A., Bardoni, B. and Pastore, A. (2006). The structure of the N-terminal domain of the fragile X mental retardation protein: a platform for protein-protein interaction. Structure 14: 21-31. Medline abstract: 16407062

Schüpbach, T. and Wieschaus, E. (1986). Germline autonomy of maternal-effect mutations altering the embryonic body pattern of Drosophila. Dev. Biol. 113: 443-448. Medline abstract: 3081391

Selenko, P., Sprangers, R., Stier, G., Bühler, D., Fischer, U. and Sattler, M. (2001). SMN tudor domain structure and its interaction with the Sm proteins. Nat. Struct. Biol. 8: 27-31. Medline abstract: 11135666

Shaw, N., et al. (2007). The multifunctional human p100 protein 'hooks' methylated ligands. Nat. Struct. Mol. Biol. [Epub ahead of print]. Medline abstract: 17632523

Sprangers, R., Groves, M. R., Sinning, I. and Sattler, M. (2003). High-resolution X-ray and NMR structures of the SMN Tudor domain: conformational variation in the binding site for symmetrically dimethylated arginine residues. J. Mol. Biol. 327: 507-520. Medline abstract: 12628254

Talbot, K., Miguel-Aliaga, I., Mohaghegh, P., Ponting, C. P. and Davies, K. E. (1998). Characterization of a gene encoding survival motor neuron (SMN)-related protein, a constituent of the spliceosome complex. Hum. Mol. Genet. 7: 2149-2156. Medline abstract: 9817934

Thomson, T. and Lasko, P. (2004). Drosophila tudor is essential for polar granule assembly and pole cell specification, but not for posterior patterning. Genesis 40: 164-170. Medline abstract: 15495201

Thomson, T. and Lasko, P. (2005). Tudor and its domains: germ cell formation from a Tudor perspective. Cell Res. 15: 281-291. Medline abstract: 15857583

Wang, C., Dickinson, L. K. and Lehmann, R. (1994). Genetics of nanos localization in Drosophila. Dev. Dyn. 199: 103-115. Medline abstract: 7515724

Yang, J., et al. (2007). Transcriptional co-activator protein p100 interacts with snRNP proteins and facilitates the assembly of the spliceosome. Nucleic Acids Res. 35(13): 4485-4494. Medline abstract: 17576664

date revised: 30 May 2008

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