核醣核酸分子參加許多的生化反應，如催化，核醣核酸編接，轉譯和轉錄的調控，和蛋白質的交互作用。生化的功能和核醣核酸的結構有高度相關。在核醣核酸後修飾作用和調控有相同功能的區域會有保留的結構或序列。雖然現有工具可以發現保留的序列根據序列的同源和排比，然而更重要的是尋找共同二級結構特徵區塊和它們的功能。我們要建構一個工具可以偵測保留的結構於核醣核酸。這個工具包涵三個部份分別是預測核醣核酸二級結構，發現重複的結構和分類重複的結構。首先用mfold來預測核醣核酸結構。接下來用後秩陣列去發現重複的結構。最後重複的結構被分類成特徵區塊根據結構長度。

RNA molecules involved with a variety of important biological processes such as catalysis, RNA splicing, regulation of transcription, translation, and protein interactions. These biological function is highly related to the structure folding of an RNA molecule. Studies in RNA such as many trans-acting non-coding RNA genes and cis-acting RNA regulatory elements show that similar functional RNA share conserved structure or sequence. Although there are tools in finding conserved sequence base on sequence homology and alignment, fining common secondary structure motif is not available. We aim to build a tool which can detect structure conservation on RNA sequences. The proposed tool contains three parts which are “predict RNA secondary structure”, “find repeat structures” and “cluster repeat structures”. First, our research use mfold to predict RNA structure. Second, our research use suffix array to find repeat structure. Finally, repeat structures are cluster to motifs by length of the structure. Some case studies are shown to demonstrate there exist structure conservation on some RNA sequence families where sequence variation on these families are high.

[1] P. Klaff, D. Riesner, and G. Steger, "RNA structure and the regulation of gene expression," Plant Mol Biol, vol. 32, pp. 89-106, 1996.
[2] S. P. Gygi, Y. Rochon, B. R. Franza, and R. Aebersold, "Correlation between protein and mRNA abundance in yeast," Mol Cell Biol, vol. 19, pp. 1720-30, 1999.
[3] N. K. Gray and M. W. Hentze, "Regulation of protein synthesis by mRNA structure," Mol Biol Rep, vol. 19, pp. 195-200, 1994.
[4] S. R. Eddy, "Non-coding RNA genes and the modern RNA world," Nat Rev Genet, vol. 2, pp. 919-29, 2001.
[5] V. A. Erdmann, M. Z. Barciszewska, M. Szymanski, A. Hochberg, N. de Groot, and J. Barciszewski, "The non-coding RNAs as riboregulators," Nucleic Acids Res, vol. 29, pp. 189-93, 2001.
[6] G. Pavesi, G. Mauri, M. Stefani, and G. Pesole, "RNAProfile: an algorithm for finding conserved secondary structure motifs in unaligned RNA sequences," Nucleic Acids Res, vol. 32, pp. 3258-69, 2004.
[7] J. Gorodkin, S. L. Stricklin, and G. D. Stormo, "Discovering common stem-loop motifs in unaligned RNA sequences," Nucleic Acids Res, vol. 29, pp. 2135-44, 2001.
[8] H. Y. Kim, T. LaVaute, K. Iwai, R. D. Klausner, and T. A. Rouault, "Identification of a conserved and functional iron-responsive element in the 5''-untranslated region of mammalian mitochondrial aconitase," J Biol Chem, vol. 271, pp. 24226-30, 1996.
[9] E. C. Theil, "The iron responsive element (IRE) family of mRNA regulators. Regulation of iron transport and uptake compared in animals, plants, and microorganisms," Met Ions Biol Syst, vol. 35, pp. 403-34, 1998.
[10] M. W. Hentze and L. C. Kuhn, "Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress," Proc Natl Acad Sci U S A, vol. 93, pp. 8175-82, 1996.
[11] J. L. T. Jeremy M. Berg, Lubert Stryer and Neil D. Clarke, Biochemistry: Michelle Julet, 2002.
[12] V. Matys, E. Fricke, R. Geffers, E. Gossling, M. Haubrock, R. Hehl, K. Hornischer, D. Karas, A. E. Kel, O. V. Kel-Margoulis, D. U. Kloos, S. Land, B. Lewicki-Potapov, H. Michael, R. Munch, I. Reuter, S. Rotert, H. Saxel, M. Scheer, S. Thiele, and E. Wingender, "TRANSFAC: transcriptional regulation, from patterns to profiles," Nucleic Acids Res, vol. 31, pp. 374-8, 2003.
[13] F. Mignone, G. Grillo, F. Licciulli, M. Iacono, S. Liuni, P. J. Kersey, J. Duarte, C. Saccone, and G. Pesole, "UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs," Nucleic Acids Res, vol. 33, pp. D141-6, 2005.
[14] C. Witwer, S. Rauscher, I. L. Hofacker, and P. F. Stadler, "Conserved RNA secondary structures in Picornaviridae genomes," Nucleic Acids Res, vol. 29, pp. 5079-89, 2001.
[15] I. L. Hofacker, M. Fekete, C. Flamm, M. A. Huynen, S. Rauscher, P. E. Stolorz, and P. F. Stadler, "Automatic detection of conserved RNA structure elements in complete RNA virus genomes," Nucleic Acids Res, vol. 26, pp. 3825-36, 1998.
[16] J. Gorodkin, L. J. Heyer, and G. D. Stormo, "Finding common sequence and structure motifs in a set of RNA sequences," Proc Int Conf Intell Syst Mol Biol, vol. 5, pp. 120-3, 1997.
[17] D. Sankoff, "Simultaneous solution of the RNA folding, alignment and protosequence problems," SIAM J., vol. 45, pp. 810-825, 1985.
[18] Y. J. Hu, "GPRM: A genetic programming approach to finding common RNA secondary structure elements," Nucleic Acids Res, vol. 31, pp. 3446-9, 2003.
[19] M. Zuker, "Mfold web server for nucleic acid folding and hybridization prediction," Nucleic Acids Res, vol. 31, pp. 3406-15, 2003.
[20] M. Zuker, "On finding all suboptimal foldings of an RNA molecule," Science, vol. 244, pp. 48-52, 1989.
[21] Y. Ding and C. E. Lawrence, "A statistical sampling algorithm for RNA secondary structure prediction," Nucleic Acids Res, vol. 31, pp. 7280-301, 2003.
[22] I. L. Hofacker, "Vienna RNA secondary structure server," Nucleic Acids Res, vol. 31, pp. 3429-31, 2003.
[23] J. Gorodkin, L. J. Heyer, and G. D. Stormo, "Finding the most significant common sequence and structure motifs in a set of RNA sequences," Nucleic Acids Res, vol. 25, pp. 3724-32, 1997.
[24] J. H. Havgaard, R. B. Lyngso, G. D. Stormo, and J. Gorodkin, "Pairwise local structural alignment of RNA sequences with sequence similarity less than 40%," Bioinformatics, vol. 21, pp. 1815-24, 2005.
[25] R. J. Klein and S. R. Eddy, "RSEARCH: finding homologs of single structured RNA sequences," BMC Bioinformatics, vol. 4, pp. 44, 2003.
[26] T. A. Brown, Genomes, 2002.
[27] R. B.-Y. a. B. Ribeiro-Neto, Modern Information Retrieval, 2001.
[28] E. W. Manber U. and Myers, "Suffix arrays: a new method for on-line string searches," SIAM J. Comput., vol. 22, pp. 935–948, 1993.
[29] J. Bentley, Programming Pearls, 2nd Edition ed: Addison-Wesley Professional; 2 edition (September 27, 1999), 1999.
[30] N. Pillai-Nair, K. H. Kim, and C. Hemenway, "Cis-acting regulatory elements in the potato virus X 3'' non-translated region differentially affect minus-strand and plus-strand RNA accumulation," J Mol Biol, vol. 326, pp. 701-20, 2003.
[31] Y. M. Hou, "The tertiary structure of tRNA and the development of the genetic code," Trends Biochem Sci, vol. 18, pp. 362-4, 1993.
[32] T. M. Lowe and S. R. Eddy, "tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence," Nucleic Acids Res, vol. 25, pp. 955-64, 1997.