Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Cell Rep. 2018 Mar 20;22(12):3217-3226. doi: 10.1016/j.celrep.2018.02.094.
In mRNA sequences, 3' UTRs are thought to contain most elements that specifically regulate localization, turnover, and translation. Although high-throughput experiments indicate that many RNA-binding proteins (RBPs) also bind 5' UTRs, much less is known about specific post-transcriptional control exerted by 5' UTRs. GLD-1 is a conserved RBP and a translational repressor with essential roles in Caenorhabditis elegans germ cell development. Previously, we showed that GLD-1 binds highly conserved sites in both 3' and 5' UTRs. Here, by targeted single-copy insertion of transgenes, we systematically tested in vivo functionality of 5' and 3' UTR binding sites individually and in combination. Our data show that sites in 5' UTRs mediate specific and strong translational repression, independent of exact position. Intriguingly, we found that the functionality of 3' UTR sites can be masked by 5' UTR sites and vice versa. We conclude that it is important to study both UTRs simultaneously.
在 mRNA 序列中，3' UTR 被认为包含大多数特异性调节定位、周转和翻译的元件。尽管高通量实验表明许多 RNA 结合蛋白（RBPs）也结合 5' UTR，但关于 5' UTR 施加的特定转录后控制知之甚少。GLD-1 是一种保守的 RBP，也是秀丽隐杆线虫生殖细胞发育所必需的翻译抑制剂。此前，我们发现 GLD-1 结合 3' 和 5' UTR 中高度保守的位点。在这里，通过靶向单拷贝插入转基因，我们系统地测试了单独和组合使用 5' 和 3' UTR 结合位点的体内功能。我们的数据表明，5' UTR 中的位点介导特异性和强翻译抑制，而与确切位置无关。有趣的是，我们发现 3' UTR 位点的功能可以被 5' UTR 位点掩盖，反之亦然。我们得出的结论是，同时研究两个 UTR 很重要。
