人類mRNA多聚腺甘酸化作用點之特徵探勘與預測

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姓名

陳昱廷(Yu-Ting Chen) 查詢紙本館藏

畢業系所

資訊工程學系

論文名稱

人類mRNA多聚腺甘酸化作用點之特徵探勘與預測
(Characterization and prediction of mRNA polyadenylation sites in human genes)

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摘要(中)

mRNA 的多聚腺甘酸化(polyadenylation)在真核細胞中是一項必要的反應，未成熟的mRNA 藉由此反應形成3 碳糖尾端，並且多方面影響了mRNA 的新陳代謝。然而由於多聚腺甘酸化對於其作用點具有多重的選擇性，其中存在著複雜的機制，至今尚未被完全了解。DNA 可以經由選擇性的多聚腺甘酸化，轉錄生成的不同蛋白質產物，藉此針對特定組織或生長時期進行調控的工作。如此機制的運作不良可能導致疾病的產生。多聚腺甘酸化的作用點需要藉由鄰近序列上或結構上的特徵得以成功被相關因子所辨識，包括某些已知的蛋白質與序列之結合。經由對多聚腺甘酸化的作用點的特徵探勘我們發展了一個可靠的預測模型，以幫助探究這項機制的奧秘。此外，我們使用現有的結構預測軟體，初步探討了RNA 二級結構對於多聚腺甘酸化的影響。我們發現一種簡單的二級結構以顯著的比例出現在作用點附近。如此一項功能性的結構特徵值得後人深入研究。

摘要(英)

mRNA polyadenylation is the essential cellular process by which most eukaryotic pre-mRNAs form their 3’ ends. It has been shown to influence many aspects of the cellular metabolism of mRNA. The complexity of mRNA polyadenylation mechanism mainly lies in the selection of poly(A) sites, since polyadenylation itself could be a regulated event. The event of alternative polyadenylation has been shown to be widespread. In this study, we developed a reliable methodology for poly(A) site prediction via bioinformatic characterization of poly(A) sites. We also conducted a series of observations on the impact of RNA structure in a preliminary step and found a significant usage of hairpin structure by using motif search tools. Thus, we suggest that in addition to the sequence pattern around poly(A)sites, there exists a widespread structural pattern employed by human mRNA polyadenylation.

關鍵字(中)

★ 多聚腺甘酸化
★ 預測

關鍵字(英)

★ poly(A) site
★ prediction
★ support vector machine
★ polyadenylation

論文目次

Chapter 1 Introduction.................................................................................................1
1.1 Background.........................................................................................................1
1.1.1 Overview of polyadenylation mechanisms...........................................................................1
1.1.2 Alternative polyadenylation......................................................................................3
1.1.3 Prediction of mRNA polyadenylation sites.........................................................................4
1.2 Motivation.........................................................................................................5
1.3 Goal...............................................................................................................5
Chapter 2 Related Works ...............................................................................................6
2.1 Sequence analysis of human poly(A) sites ..........................................................................6
2.2 Structure analysis of human poly(A) sites .........................................................................6
2.3 Existing resources of poly(A) sites ...............................................................................8
2.4 Prediction tools of human poly(A) sites ...........................................................................9
2.4.1 Polyadq .........................................................................................................9
2.4.2 Erpin............................................................................................................9
2.4.3 Polya_svm........................................................................................................9
2.5 Motif search tools of RNA secondary structure.....................................................................10
2.5.1 Sfold...........................................................................................................10
2.5.2 RNAfold.........................................................................................................10
2.5.3 RNAMotif .......................................................................................................11
Chapter 3 Materials and Methods.......................................................................................12
3.1 Materials ........................................................................................................12
3.2 Test procedure....................................................................................................13
3.3 Overview of our methodology.......................................................................................15
3.3.1 Detection of candidate PASes ...................................................................................17
3.3.2 Extraction of k-mer features ...................................................................................18
3.3.3 Characterization of sub-regions around the PAS .................................................................18
3.3.4 Detection of core elements involved in RNA secondary
structure.............................................................................................................18
3.3.5 Machine learning ...............................................................................................19
3.4 Integration of different types of features........................................................................19
Chapter 4 Results.....................................................................................................20
4.1 Characteristics of polyadenylation signals........................................................................20
4.2 Prediction of poly(A) sites by SVM................................................................................25
4.3 RNA secondary structure ..........................................................................................26
Chapter 5 Discussion..................................................................................................31
References............................................................................................................33

參考文獻

1. Brown, T.A., Genomes 2. Oxfordshire: BIOS Scientific Publishers, 2002.
2. Lewis, J.D., S.I. Gunderson, and I.W. Mattaj, The influence of 5' and 3' end structures on pre-mRNA metabolism. J Cell Sci Suppl, 1995. 19: p. 13-9.
3. Jacobson, A. and S.W. Peltz, Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. Annu Rev Biochem, 1996. 65: p. 693-739.
4. Wickens, M., P. Anderson, and R.J. Jackson, Life and death in the cytoplasm: messages from the 3' end. Curr Opin Genet Dev, 1997. 7(2): p. 220-32.
5. Colgan, D.F. and J.L. Manley, Mechanism and regulation of mRNA polyadenylation. Genes Dev, 1997. 11(21): p. 2755-66.
6. Keller, W. and L. Minvielle-Sebastia, A comparison of mammalian and yeast pre-mRNA 3'-end processing. Curr Opin Cell Biol, 1997. 9(3): p. 329-36.
7. Wahle, E. and U. Kuhn, The mechanism of 3' cleavage and polyadenylation of eukaryotic pre-mRNA. Prog Nucleic Acid Res Mol Biol, 1997. 57: p. 41-71.
8. Zhao, J., L. Hyman, and C. Moore, Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis. Microbiol Mol Biol Rev, 1999. 63(2): p. 405-45.
9. Edmonds, M., A history of poly A sequences: from formation to factors to function. Prog Nucleic Acid Res Mol Biol, 2002. 71: p. 285-389.
10. Edwalds-Gilbert, G., K.L. Veraldi, and C. Milcarek, Alternative poly(A) site selection in complex transcription units: means to an end? Nucleic Acids Res, 1997. 25(13): p. 2547-61.
11. Beaudoing, E. and D. Gautheret, Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data. Genome Res, 2001. 11(9): p. 1520-6.
12. Graber, J.H., et al., In silico detection of control signals: mRNA 3'-end-processing sequences in diverse species. Proc Natl Acad Sci U S A, 1999. 96(24): p. 14055-60.
13. Beaudoing, E., et al., Patterns of variant polyadenylation signal usage in human genes. Genome Res, 2000. 10(7): p. 1001-10.
14. MacDonald, C.C. and J.L. Redondo, Reexamining the polyadenylation signal: were we wrong about AAUAAA? Mol Cell Endocrinol, 2002. 190(1-2): p. 1-8.
15. Tian, B., et al., A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res, 2005. 33(1): p. 201-12.
16. Legendre, M. and D. Gautheret, Sequence determinants in human polyadenylation site selection. BMC Genomics, 2003. 4(1): p. 7.
17. Zarudnaya, M.I., et al., Downstream elements of mammalian pre-mRNA polyadenylation signals: primary, secondary and higher-order structures. Nucleic Acids Res, 2003. 31(5): p. 1375-86.
18. Wahle, E., 3'-end cleavage and polyadenylation of mRNA precursors. Biochim Biophys Acta, 1995. 1261(2): p. 183-94.
19. Carswell, S. and J.C. Alwine, Efficiency of utilization of the simian virus 40 late polyadenylation site: effects of upstream sequences. Mol Cell Biol, 1989. 9(10): p. 4248-58.
20. Brown, P.H., L.S. Tiley, and B.R. Cullen, Efficient polyadenylation within the human immunodeficiency virus type 1 long terminal repeat requires flanking U3-specific sequences. J Virol, 1991. 65(6): p. 3340-3.
21. Valsamakis, A., et al., The human immunodeficiency virus type 1 polyadenylylation signal: a 3' long terminal repeat element upstream of the AAUAAA necessary for efficient polyadenylylation. Proc Natl Acad Sci U S A, 1991. 88(6): p. 2108-12.
22. Moreira, A., et al., Upstream sequence elements enhance poly(A) site efficiency of the C2 complement gene and are phylogenetically conserved. EMBO J, 1995. 14(15): p. 3809-19.
23. Arhin, G.K., et al., Downstream sequence elements with different affinities for the hnRNP H/H' protein influence the processing efficiency of mammalian polyadenylation signals. Nucleic Acids Res, 2002. 30(8): p. 1842-50.
24. Natalizio, B.J., et al., Upstream elements present in the 3'-untranslated region of collagen genes influence the processing efficiency of overlapping polyadenylation signals. J Biol Chem, 2002. 277(45): p. 42733-40.
25. Hall-Pogar, T., et al., Alternative polyadenylation of cyclooxygenase-2. Nucleic Acids Res, 2005. 33(8): p. 2565-79.
26. Bennett, C.L., et al., A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA-->AAUGAA) leads to the IPEX syndrome. Immunogenetics, 2001. 53(6): p. 435-9.
27. Gehring, N.H., et al., Increased efficiency of mRNA 3' end formation: a new genetic mechanism contributing to hereditary thrombophilia. Nat Genet, 2001. 28(4): p. 389-92.
28. Yan, J. and T.G. Marr, Computational analysis of 3'-ends of ESTs shows four classes of alternative polyadenylation in human, mouse, and rat. Genome Res, 2005. 15(3): p. 369-75.
29. Maniatis, T. and R. Reed, An extensive network of coupling among gene expression machines. Nature, 2002. 416(6880): p. 499-506.
30. Neugebauer, K.M., On the importance of being co-transcriptional. J Cell Sci, 2002. 115(Pt 20): p. 3865-71.
31. Calvo, O. and J.L. Manley, Strange bedfellows: polyadenylation factors at the promoter. Genes Dev, 2003. 17(11): p. 1321-7.
32. Proudfoot, N., New perspectives on connecting messenger RNA 3' end formation to transcription. Curr Opin Cell Biol, 2004. 16(3): p. 272-8.
33. Zhang, H., J.Y. Lee, and B. Tian, Biased alternative polyadenylation in human tissues. Genome Biol, 2005. 6(12): p. R100.
34. Takagaki, Y., et al., The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation. Cell, 1996. 87(5): p. 941-52.
35. Brockman, J.M., et al., PACdb: PolyA Cleavage Site and 3'-UTR Database. Bioinformatics, 2005. 21(18): p. 3691-3.
36. Tabaska, J.E. and M.Q. Zhang, Detection of polyadenylation signals in human DNA sequences. Gene, 1999. 231(1-2): p. 77-86.
37. Hans, H. and J.C. Alwine, Functionally significant secondary structure of the simian virus 40 late polyadenylation signal. Mol Cell Biol, 2000. 20(8): p. 2926-32.
38. Sittler, A., H. Gallinaro, and M. Jacob, The secondary structure of the adenovirus-2 L4 polyadenylation domain: evidence for a hairpin structure exposing the AAUAAA signal in its loop. J Mol Biol, 1995. 248(3): p. 525-40.
39. Klasens, B.I., et al., The ability of the HIV-1 AAUAAA signal to bind polyadenylation factors is controlled by local RNA structure. Nucleic Acids Res,1999. 27(2): p. 446-54.
40. Wahle, E. and U. Ruegsegger, 3'-End processing of pre-mRNA in eukaryotes. FEMS Microbiol Rev, 1999. 23(3): p. 277-95.
41. Phillips, C., C.B. Kyriakopoulou, and A. Virtanen, Identification of a stem-loop structure important for polyadenylation at the murine IgM secretory poly(A) site. Nucleic Acids Res, 1999. 27(2): p. 429-38.
42. Proudfoot, N., Poly(A) signals. Cell, 1991. 64(4): p. 671-4.
43. Lee, J.Y., et al., PolyA_DB 2: mRNA polyadenylation sites in vertebrate genes. Nucleic Acids Res, 2007. 35(Database issue): p. D165-8.
44. Lambert, A., et al., The ERPIN server: an interface to profile-based RNA motif identification. Nucleic Acids Res, 2004. 32(Web Server issue): p. W160-5.
45. Cheng, Y., R.M. Miura, and B. Tian, Prediction of mRNA polyadenylation sites by support vector machine. Bioinformatics, 2006. 22(19): p. 2320-5.
46. Hu, J., et al., Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation. RNA, 2005. 11(10): p. 1485-93.
47. Ding, Y., C.Y. Chan, and C.E. Lawrence, Sfold web server for statistical folding and rational design of nucleic acids. Nucleic Acids Res, 2004. 32(Web Server issue): p. W135-41.
48. Hofacker, I.L., Vienna RNA secondary structure server. Nucleic Acids Res, 2003. 31(13): p. 3429-31.
49. Zuker, M. and P. Stiegler, Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res, 1981. 9(1): p. 133-148.
50. McCaskill, J.S., The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers, 1990. 29(6-7): p. 1105-19.
51. Hofacker, I.L., et al., Fast folding and comparison of RNA secondary structures. Monatshefte fur Chemie/Chemical Monthly, 1994. 125(2): p. 167-188.
52. Macke, T.J., et al., RNAMotif, an RNA secondary structure definition and search algorithm. Nucleic Acids Res, 2001. 29(22): p. 4724-35.
53. Pruitt, K.D. and D.R. Maglott, RefSeq and LocusLink: NCBI gene-centered resources. Nucleic Acids Res, 2001. 29(1): p. 137-40.
54. Mignone, F., et al., UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs. Nucleic Acids Res, 2005. 33(Database issue): p. D141-6.
55. Liu, H., et al., An in-silico method for prediction of polyadenylation signals in human sequences. Genome Inform, 2003. 14: p. 84-93.
56. Zien, A., et al., Engineering support vector machine kernels that recognize translation initiation sites. Bioinformatics, 2000. 16(9): p. 799-807.
57. Zhang, M.Q., Discriminant analysis and its application in DNA sequence motif recognition. Brief Bioinform, 2000. 1(4): p. 331-42.
58. Zhang, X.H., et al., Sequence information for the splicing of human pre-mRNA identified by support vector machine classification. Genome Res, 2003. 13(12): p. 2637-50.
59. Yeo, G., et al., Variation in alternative splicing across human tissues. Genome Biol, 2004. 5(10): p. R74.
60. Shaw, G. and R. Kamen, A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell, 1986. 46(5): p. 659-67.
61. Chen, C.Y. and A.B. Shyu, AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci, 1995. 20(11): p. 465-70.
62. Tian, B., Z. Pan, and J.Y. Lee, Widespread mRNA polyadenylation events in introns indicate dynamic interplay between polyadenylation and splicing. Genome Res, 2007. 17(2): p. 156-65.

指導教授

洪炯宗(Jorng-Tzong Horng)

審核日期

2008-7-19

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