系統化重建人類基因體中微小核醣核酸的調控網路

Abstract

微小核醣核酸(microRNA)具有調控人體內重要生理反應的功能，近年來更被發現與疾病甚至癌症生成有關。由於它是藉由抑制標靶基因的表現來達成作用機轉，現今研究大部分著重在尋找其標靶基因，或開發許多生物資訊工具及資料庫來做相關預測和資料蒐集;然而，在微小核醣核酸本身如何被轉錄和調控的範疇裡，卻鮮少被生物學家著墨。為此，我們設計了一套系統化的分析方法，從基因轉錄啟始點(transcriptional start site)的辨識，啟動子(promoter)的序列分析，進而探勘可能調控微小核醣核酸基因的轉錄因子(Transcription factor)，並結合經實驗驗證的標靶基因群，建立完整的調控網路以及功能性註解。我們也以hsa-miR-122這個重要的微小核醣核酸作為範例，證明此研究方法的可行性和可信度，並解釋了生物學家未解的生理現象。希望透過系統化重建人類基因體中微小核醣核酸的調控網路，能提供有用而完整的資訊，充分了解微小核醣核酸在人體內扮演的角色，供病理實驗及臨床上研究的重要參考依據。

MicroRNAs (miRNAs) are critical small non-coding RNAs that regulate gene expression by hybridizing to the 3’-untranslated regions (3’-UTR) of target mRNAs, negatively controlling diverse biological processes at posttranscriptional level. Given the significance of miRNA functions and its role in gene regulation, how miRNA genes are transcriptionally regulated receives considerable attention as well as target recognition. The purpose of this study is to create a systematic approach to reconstruct miRNA regulatory networks in human genome, offering valuable information to comprehensively understand the molecular roles of human miRNAs. Through the procedures of TSS/promoter identification, detection of cis- and trans- elements, discovery of miRNA-mediated target genes, and functional annotation, we successfully inferred regulatory networks for human miRNAs. In addition, liver-specific hsa-miR-122 was selected as a case study to evaluate the performance of the research processes, showing good feasibility and reliability to explore undiscovered bio-mechanisms for advanced studies and clinical research.