人類胚胎選擇性多腺苷酸化之動態分析

Abstract

Pre-mRNA的選擇性多腺苷酸化會造成mature mRNA的3端非轉錄區域(3’-UTR)的長度變化，並進一步影響microRNA對mature mRNA的調控。之前的研究已經發現，癌細胞相較於正常細胞傾向於擁有較短的3端非轉錄區域，一般相信這個現象是癌細胞為了躲避microRNA的調控而產生。在這份研究中，我們對這個現象延伸出一個相對的想法─探討在人類早期胚胎發育過程中，3端非轉錄區域的長度變化。與癌細胞相反的，在人類胚胎發育的早期，3端非轉錄區域隨著發育時間傾向變長，同時我們也發現3端非轉錄區域變長的mRNA與其基因表現量呈現出負相關。更進一步的功能富集分析(Functional Enrichment Analysis)結果，也顯示出3端非轉錄區域長度變化的確與發育機制有關。我們也將3端非轉錄區域長度變化的概念放到lncRNA中，亦發現lncRNA的3端非轉錄區域隨著發育時間傾向變長。

Alternative PolyAdenylation (APA) causes the variation of 3’UTR length and affects the regulation of microRNAs. Previous study has shown that cancer cell tend to have shorter 3’UTR length compare to normal cell. A plausible explains is to escape the regulation of microRNAs. In this article, we extend the concept to the opposite situation, the change of 3’UTR length in human preimplantation embryo development. Unlike cancer cell, during early development, 3’UTR tend to become longer and the gene expression has shown negative correlation to the 3’UTR length. Moreover, the functional enrichment results shown that the change of length is part of the development mechanism. We also introduce this concept of 3’UTR length variation to lncRNA. Found out that lncRNA tend to become longer during embryo development, too.