分析微小核醣核酸與目標基因間的作用關係及尋找標靶基因的應用

微小核醣核酸(microRNA/miRNA)是一段長度約為22核苷酸的非編碼的核醣核酸分子，它們可藉由與基因的結合來調控基因的表現，研究發現微小核醣核酸調控許多的基因與細胞功能有關，例如，細胞凋零、細胞分化與細胞發育。之前的文獻認為30%或更多的人類基因受到微小核醣核酸的調控。由於微小核醣核酸在生物的重要性，所以許多相關的資料庫及工具被開發出來。本文主要是分析微小核醣核酸與其目標基因間的作用關係，並探討此關係的序列及結構特徵，根據此分析結果開發新的方法或整合系統研究微小核醣核酸的功能。我們總共分析了1,524個實驗驗證過的微小核醣核酸與目標基因的作用關係，並以此作為評估預測正確性的資料。通過分析已知的微小核醣酸與其目標基因的作用關係，我們可以獲得其序列與結構上的特徵。這些分析與實驗已知的資料對於尋找標靶基因工具的開發是很重要，且生物學家可以透過此結果選擇適當的預測工具。此外，還有其他因素會影響微小核醣核酸是否會與目標基因結合，例如，核醣核酸結合的蛋白質(RNA誘導沉默複合體)、微小核醣核酸及信息核醣核酸的濃度。未來我們會將這些因素加入分析微小核醣核酸與目標基因的作用關係。

關鍵字

微小核醣核酸；微小核醣核酸目標基因； miRTarBase

並列摘要

MicroRNAs (miRNAs) are small non-coding RNA molecules (~ 22-nt) that can bind to one or more target sites on gene transcript to negatively regulate protein expression and thus control numerous cellular mechanisms. Recent work supports miRNAs downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Previous research has suggested that miRNAs regulate 30% or more of the human protein-coding genes. As the important roles of miRNAs, there were multiple databases storing the miRNA-target interactions (MTIs) identified using different tools. The aim of this work is to systematically analyze the miRNA-target interactions and assess the function of miRNA by developing new methods and resources. In this study, we analyzed 1,524 experimentally verified miRNA-target interactions with strong evidence support in human and elucidate which the more accurate microRNA target prediction database is. Through analyzing the verified MTIs, we could get the overview of relative contribution of sequence and structure features in miRNA targeting. Those analyses are important for identifying putative miRNA targets and are very useful for biologist to choose the proper tool for miRNA research. There are still other factors such as RNA binding protein (RISC), the concentration of miRNA and mRNA, playing an important role in the identification of miRNA-target interaction. We need take into account these factors in future works in order to develop the more reliable miRNA target prediction resources.

並列關鍵字

microRNA ； miRNA ； MTI ； miRNA-target interaction ； miRTarBase

參考文獻

1. Wightman, B., Ha, I. and Ruvkun, G. (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 75, 855-862.

2. Griffiths-Jones, S., Grocock, R.J., van Dongen, S., Bateman, A. and Enright, A.J. (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res, 34, D140-144.

4. Hsu, P.W., Huang, H.D., Hsu, S.D., Lin, L.Z., Tsou, A.P., Tseng, C.P., Stadler, P.F., Washietl, S. and Hofacker, I.L. (2006) miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes. Nucleic Acids Res, 34, D135-139.

5. Hsu, S.D., Lin, F.M., Wu, W.Y., Liang, C., Huang, W.C., Chan, W.L., Tsai, W.T., Chen, G.Z., Lee, C.J., Chiu, C.M. et al. (2011) miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic acids research, 39, D163-169.

6. Hsu, J.B., Chiu, C.M., Hsu, S.D., Huang, W.Y., Chien, C.H., Lee, T.Y. and Huang, H.D. (2011) miRTar: an integrated system for identifying miRNA-target interactions in Human. BMC Bioinformatics, 12, 300.

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分析微小核醣核酸與目標基因間的作用關係及尋找標靶基因的應用

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