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研究生:侯柏存
研究生(外文):Po-Tsun
論文名稱:斑馬魚胚胎發育時期PRMT1基因表現與功能分析
論文名稱(外文):Developmental Expression and Functional Analysis of PRMT1 Gene in Zebrafish
指導教授:李娟李娟引用關係
指導教授(外文):Chuan Li
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:生物醫學科學學系碩士班
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:75
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蛋白質精胺酸甲基化是常見的轉譯後修飾,將 S-adenosyl-L-methionine (AdoMet)上的甲基集團轉到氮原子上。蛋白質精胺酸甲基轉移酶(PRMT)會調控細胞的訊息傳遞、轉錄、RNA 運輸以及 RNA 剪接等。人類細胞中PRMT1 所催化的精胺酸甲基化反應約佔85 %。PRMT1 缺乏的老鼠胚胎會在 6.5 天的時候死亡。斑馬魚( Danio rerio) 已經成為研究胚胎發育、脊椎動物的遺傳以及人類疾病的重要的模式動物。為了要再更深入了解 prmt1 於胚胎發育的角色,我們以斑馬魚為實驗對象探討 prmt1 於胚胎發育時的功能。斑馬魚的 prmt1 胺基酸序列與人類的相似度為 96 ﹪ 可轉譯出341個胺基酸。取斑馬魚胚胎萃取液經由西方墨點法的分析可證實的確有PRMT1蛋白表現。此外,利用全體原位雜交的方法偵測到 prmt1 自合子期至幼魚早期都有表現。發現 prmt1 在嗅球、眼頂蓋、中腦、小腦、後腦、中後腦交界處以及下巴的咽喉腮弓等部位的細胞上都有明顯的訊號表現。接著以prmt1 以反意 morpholino 將斑馬魚胚胎之 prmt1 抑制,造成了一些 morphant 的缺陷包括:尾巴微彎、體型彎曲、體軸變短、脊椎彎曲、卵黃形狀改變等。以上這些實驗結果顯示了PRMT1對於斑馬魚胚胎發育之影響。

Protein arginine methylation is a widespread post translational modification that transfers methyl groups from S-adenosyl-L
-methionine (AdoMet) to the guanidino nitrogen atoms of arginine residues in the living cells. Protein arginine methyltransferases (PRMT) has been reported to regulate signal transduction, transcription, RNA transport, and RNA splicing. PRMT1 is the predominant arginine methyltransferases in human cell, responsible for at least 85% of all arginine methylation reactions. PRMT1 null mice embryos die at approximately embryonic day 6.5. Zebrafish ( Danio rerio) has recently emerged as an important model organism for studies of embryonic development, vertebrate genetics and human disease. To elucidate the role of PRMT1 during embryogenesis, we use zebrafish as our model system. The zebrafish PRMT1 ORF encodes a 341 amino-acid polypeptide which shares 96% homologies to human PRMT1. Western blot analyses of zebrafish embryo extracts confirmed the expression of PRMT1 protein in zebrafish. During embryonic development, prmt1 transcripts were detected from the zygote period to the early larva stage. Whole-mount in situ hybridization revealed that prmt1 was expressed in most parts of the brain including olfactory bulbs, optic tectum, mesencephalon, cerebellum, hidbrain, middle hind-brain boundary and pharyngeal arches during zebrafish embryogenesis. Knocking down of prmt1 by antisense morpholino oligo results in several morphological defects in embryos in a dose-dependent manner, including malformed tail, shortened and curved body axes, myeloid,yolk shape of change. These data clearly demonstrate a role for PRMT1 in specific developmental processes of zebrafish.


中文摘要.............................................. 1
英文摘要.............................................. 2
第一章 序論........................................... 4
第二章 實驗材料與方法.................................13
第三章 研究結果...................................... 26
第四章 討論.......................................... 33
參考文獻............................................. 37
圖表與圖表說明....................................... 43
附圖................................................. 59


1.Aletta, J. M., T. R. Cimato, and M. J. Ettinger. 1998. Protein methylation: a signal event in post-translational modification. Trends Biochem Sci 23:89-91.
2.Altschuler, L., J. O. Wook, D. Gurari, J. Chebath, and M. Revel. 1999. Involvement of receptor-bound protein methyltransferase PRMT1 in antiviral and antiproliferative effects of type I interferons. J Interferon Cytokine Res 19:189-95.
3.Bedford, M. T., A. Frankel, M. B. Yaffe, S. Clarke, P. Leder, and S. Richard. 2000. Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains. J Biol Chem 275:16030-6.
4.Bedford, M. T., and S. Richard. 2005. Arginine methylation an emerging regulator of protein function. Mol Cell 18:263-72.
5.Birney, E., S. Kumar, and A. R. Krainer. 1993. Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors. Nucleic Acids Res 21:5803-16.
6.Boulanger, M. C., T. B. Miranda, S. Clarke, M. Di Fruscio, B. Suter, P. Lasko, and S. Richard. 2004. Characterization of the Drosophila protein arginine methyltransferases DART1 and DART4. Biochem J 379:283-9.
7.Branscombe, T. L., A. Frankel, J. H. Lee, J. R. Cook, Z. Yang, S. Pestka, and S. Clarke. 2001. PRMT5 (Janus kinase-binding protein 1) catalyzes the formation of symmetric dimethylarginine residues in proteins. J Biol Chem 276:32971-6.
8.Chen, D., H. Ma, H. Hong, S. S. Koh, S. M. Huang, B. T. Schurter, D. W. Aswad, and M. R. Stallcup. 1999. Regulation of transcription by a protein methyltransferase. Science 284:2174-7.
9.Chen, S. L., K. A. Loffler, D. Chen, M. R. Stallcup, and G. E. Muscat. 2002. The coactivator-associated arginine methyltransferase is necessary for muscle differentiation: CARM1 coactivates myocyte enhancer factor-2. J Biol Chem 277:4324-33.
10.Cook, J. R., J. H. Lee, Z. H. Yang, C. D. Krause, N. Herth, R. Hoffmann, and S. Pestka. 2006. FBXO11/PRMT9, a new protein arginine methyltransferase, symmetrically dimethylates arginine residues. Biochem Biophys Res Commun 342:472-81.
11.Corey, D. R., and J. M. Abrams. 2001. Morpholino antisense oligonucleotides: tools for investigating vertebrate development. Genome Biol 2:REVIEWS1015.
12.Cote, J., F. M. Boisvert, M. C. Boulanger, M. T. Bedford, and S. Richard. 2003. Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1. Mol Biol Cell 14:274-87.
13.Dong, C. W., Y. B. Zhang, A. J. Lu, R. Zhu, F. T. Zhang, Q. Y. Zhang, and J. F. Gui. 2007. Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection. Fish Shellfish Immunol 22:380-93.
14.Ekker, S. C., and J. D. Larson. 2001. Morphant technology in model developmental systems. Genesis 30:89-93.
15.Fabbrizio, E., S. El Messaoudi, J. Polanowska, C. Paul, J. R. Cook, J. H. Lee, V. Negre, M. Rousset, S. Pestka, A. Le Cam, and C. Sardet. 2002. Negative regulation of transcription by the type II arginine methyltransferase PRMT5. EMBO Rep 3:641-5.
16.Frankel, A., N. Yadav, J. Lee, T. L. Branscombe, S. Clarke, and M. T. Bedford. 2002. The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity. J Biol Chem 277:3537-43.
17.Friesen, W. J., S. Paushkin, A. Wyce, S. Massenet, G. S. Pesiridis, G. Van Duyne, J. Rappsilber, M. Mann, and G. Dreyfuss. 2001. The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Mol Cell Biol 21:8289-300.
18.Gary, J. D., and S. Clarke. 1998. RNA and protein interactions modulated by protein arginine methylation. Prog Nucleic Acid Res Mol Biol 61:65-131.
19.Gary, J. D., W. J. Lin, M. C. Yang, H. R. Herschman, and S. Clarke. 1996. The predominant protein-arginine methyltransferase from Saccharomyces cerevisiae. J Biol Chem 271:12585-94.
20.Hung, C. M., and C. Li. 2004. Identification and phylogenetic analyses of the protein arginine methyltransferase gene family in fish and ascidians. Gene 340:179-87.
21.Hyun, Y. L., D. B. Lew, S. H. Park, C. W. Kim, W. K. Paik, and S. Kim. 2000. Enzymic methylation of arginyl residues in -gly-arg-gly- peptides. Biochem J 348 Pt 3:573-8.
22.Katsanis, N., M. L. Yaspo, and E. M. Fisher. 1997. Identification and mapping of a novel human gene, HRMT1L1, homologous to the rat protein arginine N-methyltransferase 1 (PRMT1) gene. Mamm Genome 8:526-9.
23.Kim, S., B. M. Merrill, R. Rajpurohit, A. Kumar, K. L. Stone, V. V. Papov, J. M. Schneiders, W. Szer, S. H. Wilson, W. K. Paik, and K. R. Williams. 1997. Identification of N(G)-methylarginine residues in human heterogeneous RNP protein A1: Phe/Gly-Gly-Gly-Arg-Gly-Gly-Gly/Phe is a preferred recognition motif. Biochemistry 36:5185-92.
24.Kimmel, C. B., W. W. Ballard, S. R. Kimmel, B. Ullmann, and T. F. Schilling. 1995. Stages of embryonic development of the zebrafish. Dev Dyn 203:253-310.
25.Koh, S. S., H. Li, Y. H. Lee, R. B. Widelitz, C. M. Chuong, and M. R. Stallcup. 2002. Synergistic coactivator function by coactivator-associated arginine methyltransferase (CARM) 1 and beta-catenin with two different classes of DNA-binding transcriptional activators. J Biol Chem 277:26031-5.
26.Krause, C. D., Z. H. Yang, Y. S. Kim, J. H. Lee, J. R. Cook, and S. Pestka. 2007. Protein arginine methyltransferases: evolution and assessment of their pharmacological and therapeutic potential. Pharmacol Ther 113:50-87.
27.Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-5.
28.Lee, D. Y., C. Teyssier, B. D. Strahl, and M. R. Stallcup. 2005. Role of protein methylation in regulation of transcription. Endocr Rev 26:147-70.
29.Lee, J., and M. T. Bedford. 2002. PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays. EMBO Rep 3:268-73.
30.Lee, J., J. Sayegh, J. Daniel, S. Clarke, and M. T. Bedford. 2005. PRMT8, a new membrane-bound tissue-specific member of the protein arginine methyltransferase family. J Biol Chem 280:32890-6.

31.Lee, J. H., J. R. Cook, Z. H. Yang, O. Mirochnitchenko, S. I. Gunderson, A. M. Felix, N. Herth, R. Hoffmann, and S. Pestka. 2005. PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J Biol Chem 280:3656-64.
32.Li, H., S. Park, B. Kilburn, M. A. Jelinek, A. Henschen-Edman, D. W. Aswad, M. R. Stallcup, and I. A. Laird-Offringa. 2002. Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. Coactivator-associated arginine methyltransferase. J Biol Chem 277:44623-30.
33.Lin, W. J., J. D. Gary, M. C. Yang, S. Clarke, and H. R. Herschman. 1996. The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase. J Biol Chem 271:15034-44.
34.McBride, A. E., and P. A. Silver. 2001. State of the arg: protein methylation at arginine comes of age. Cell 106:5-8.
35.McBride, A. E., V. H. Weiss, H. K. Kim, J. M. Hogle, and P. A. Silver. 2000. Analysis of the yeast arginine methyltransferase Hmt1p/Rmt1p and its in vivo function. Cofactor binding and substrate interactions. J Biol Chem 275:3128-36.
36.Meister, G., C. Eggert, D. Buhler, H. Brahms, C. Kambach, and U. Fischer. 2001. Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln. Curr Biol 11:1990-4.
37.Miranda, T. B., M. Miranda, A. Frankel, and S. Clarke. 2004. PRMT7 is a member of the protein arginine methyltransferase family with a distinct substrate specificity. J Biol Chem 279:22902-7.
38.Mowen, K. A., J. Tang, W. Zhu, B. T. Schurter, K. Shuai, H. R. Herschman, and M. David. 2001. Arginine methylation of STAT1 modulates IFNalpha/beta-induced transcription. Cell 104:731-41.
39.Najbauer, J., B. A. Johnson, A. L. Young, and D. W. Aswad. 1993. Peptides with sequences similar to glycine, arginine-rich motifs in proteins interacting with RNA are efficiently recognized by methyltransferase(s) modifying arginine in numerous proteins. J Biol Chem 268:10501-9.


40.Pawlak, M. R., C. A. Scherer, J. Chen, M. J. Roshon, and H. E. Ruley. 2000. Arginine N-methyltransferase 1 is required for early postimplantation mouse development, but cells deficient in the enzyme are viable. Mol Cell Biol 20:4859-69.
41.Pollack, B. P., S. V. Kotenko, W. He, L. S. Izotova, B. L. Barnoski, and S. Pestka. 1999. The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity. J Biol Chem 274:31531-42.
42.Scorilas, A., M. H. Black, M. Talieri, and E. P. Diamandis. 2000. Genomic organization, physical mapping, and expression analysis of the human protein arginine methyltransferase 1 gene. Biochem Biophys Res Commun 278:349-59.
43.Scott, H. S., S. E. Antonarakis, M. D. Lalioti, C. Rossier, P. A. Silver, and M. F. Henry. 1998. Identification and characterization of two putative human arginine methyltransferases (HRMT1L1 and HRMT1L2). Genomics 48:330-40.
44.Smith, J. J., K. P. Rucknagel, A. Schierhorn, J. Tang, A. Nemeth, M. Linder, H. R. Herschman, and E. Wahle. 1999. Unusual sites of arginine methylation in Poly(A)-binding protein II and in vitro methylation by protein arginine methyltransferases PRMT1 and PRMT3. J Biol Chem 274:13229-34.
45.Summerton, J. 1999. Morpholino antisense oligomers: the case for an RNase H-independent structural type. Biochim Biophys Acta 1489:141-58.
46.Tang, J., A. Frankel, R. J. Cook, S. Kim, W. K. Paik, K. R. Williams, S. Clarke, and H. R. Herschman. 2000. PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells. J Biol Chem 275:7723-30.
47.Tang, J., J. D. Gary, S. Clarke, and H. R. Herschman. 1998. PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specificity, and regulation. J Biol Chem 273:16935-45.
48.Tang, J., P. N. Kao, and H. R. Herschman. 2000. Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3. J Biol Chem 275:19866-76.
49.Wada, K., K. Inoue, and M. Hagiwara. 2002. Identification of methylated proteins by protein arginine N-methyltransferase 1, PRMT1, with a new expression cloning strategy. Biochim Biophys Acta 1591:1-10.
50.Wang, Y. C., C. Li, M. L. Lin, W. H. Lin, and S. Y. Li. 2000. Molecular diagnosis of fragile X syndrome and distribution of CGG repeats in the FMR-1 gene in Taiwanese. J Formos Med Assoc 99:402-7.
51.Wells, J. M., and D. A. Melton. 1999. Vertebrate endoderm development. Annu Rev Cell Dev Biol 15:393-410.
52.Westerfield, M. 2000. The Zebrafish Book.
53.Xu, W., H. Chen, K. Du, H. Asahara, M. Tini, B. M. Emerson, M. Montminy, and R. M. Evans. 2001. A transcriptional switch mediated by cofactor methylation. Science 294:2507-11.
54.Yadav, N., J. Lee, J. Kim, J. Shen, M. C. Hu, C. M. Aldaz, and M. T. Bedford. 2003. Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice. Proc Natl Acad Sci U S A 100:6464-8.
55.Yoshimoto, T., M. Boehm, M. Olive, M. F. Crook, H. San, T. Langenickel, and E. G. Nabel. 2006. The arginine methyltransferase PRMT2 binds RB and regulates E2F function. Exp Cell Res 312:2040-53.
56.Zhang, X., L. Zhou, and X. Cheng. 2000. Crystal structure of the conserved core of protein arginine methyltransferase PRMT3. Embo J 19:3509-19.
57.Zhu, W., T. Mustelin, and M. David. 2002. Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase. J Biol Chem 277:35787-90.
58.Zobel-Thropp, P., J. D. Gary, and S. Clarke. 1998. delta-N-methylarginine is a novel posttranslational modification of arginine residues in yeast proteins. J Biol Chem 273:29283-6.
59.Zon, L. I. 1999. Zebrafish: a new model for human disease. Genome Res 9:99-100.


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