Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development
Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development
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DOI：
10.1073/pnas.0900028106
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发表时间：
2009-04-28
影响因子：
11.1
通讯作者：
Tian, Bin
中科院分区：
文献类型：
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作者：
Ji, Zhe;Lee, Ju Youn;Tian, Bin
mRNA的3 '非翻译区（3' UTR）包含用于基因表达的转录后调节的顺式作用元件。在这里，我们报告说，小鼠基因倾向于表达的mRNA与较长的3 'UTR胚胎发育的进展。这种全局调节由交替的多聚腺苷酸化控制，并与器官发生的起始和胚胎发育的各个方面（包括形态发生、分化和增殖）协调。以C2C12成肌细胞为模型，我们在体外重现了这一过程，发现3'UTR延长可能是由于mRNA多聚腺苷酸化活性减弱所致。由于替代3 'UTR序列通常比组成型序列更长，并且具有更高的Au含量，因此我们的研究结果表明，3' UTR的延长可以显著增强胚胎发育期间基因表达的转录后控制，例如microRNA介导的调控。
The 3' untranslated regions (3' UTRs) of mRNAs contain cis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3' UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3' UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3' UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3' UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.