Mainieri Avantika, Haig David
Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street, Cambridge, MA 02138, USA.
Evol Med Public Health. 2018 Mar 16;2018(1):82-91. doi: 10.1093/emph/eoy008. eCollection 2018.
The insulin-like growth factor (IGF) signaling system is a major arena of intragenomic conflict over embryonic growth between imprinted genes of maternal and paternal origin and the IGF type 1 receptor (IGF1R) promotes proliferation of many human cancers. The 3'-untranslated region (3'-UTR) of the mouse mRNA is targeted by miR-675-3p derived from the imprinted long noncoding RNA. We undertook a comparative sequence analysis of vertebrate 3'-UTRs to determine the evolutionary history of miR-675 target sequences and to identify conserved features that are likely to be involved in post-transcriptional regulation of IGF1R translation.
Sequences of 3'-UTRs were obtained from public databases and analyzed using publicly available algorithms.
A very long 3'-UTR is a conserved feature of vertebrate mRNAs. We found that some ancient microRNAs, such as let-7 and mir-182, have predicted binding sites that are conserved between cartilaginous fish and mammals. One very conserved region is targeted by multiple, maternally expressed imprinted microRNAs that appear to have evolved more recently than the targeted sequences.
The conserved structures we identify in the 3'-UTR are strong candidates for regulating cell proliferation during development and carcinogenesis. These conserved structures are now targeted by multiple imprinted microRNAs. These observations emphasize the central importance of IGF signaling pathways in the mediation of intragenomic conflicts over embryonic growth and identify possible targets for therapeutic interventions in cancer.
胰岛素样生长因子（IGF）信号系统是母源和父源印记基因之间关于胚胎生长的基因组内冲突的主要场所，并且IGF 1型受体（IGF1R）促进多种人类癌症的增殖。小鼠mRNA的3'非翻译区（3'-UTR）被源自印记长非编码RNA的miR-675-3p靶向。我们对脊椎动物的3'-UTR进行了比较序列分析，以确定miR-675靶序列的进化史，并识别可能参与IGF1R翻译后转录调控的保守特征。
从公共数据库中获取3'-UTR的序列，并使用公开可用的算法进行分析。
非常长的3'-UTR是脊椎动物mRNA的一个保守特征。我们发现一些古老的微小RNA，如let-7和mir-182，具有在软骨鱼和哺乳动物之间保守的预测结合位点。一个非常保守的区域被多个母源表达的印记微小RNA靶向，这些微小RNA似乎比靶向序列进化得更近。
我们在3'-UTR中鉴定出的保守结构是在发育和致癌过程中调节细胞增殖的有力候选者。这些保守结构现在被多个印记微小RNA靶向。这些观察结果强调了IGF信号通路在介导胚胎生长的基因组内冲突中的核心重要性，并确定了癌症治疗干预的可能靶点。
