Max Planck Institute for Brain Research, Frankfurt am Main, Germany.
Max Planck Institute for Brain Research, Frankfurt am Main, Germany.
Neuron. 2018 May 2;98(3):495-511.e6. doi: 10.1016/j.neuron.2018.03.030. Epub 2018 Apr 12.
Neurons localize mRNAs near synapses where their translation can be regulated by synaptic demand and activity. Differences in the 3' UTRs of mRNAs can change their localization, stability, and translational regulation. Using 3' end RNA sequencing of microdissected rat brain slices, we discovered a huge diversity in mRNA 3' UTRs, with many transcripts showing enrichment for a particular 3' UTR isoform in either somata or the neuropil. The 3' UTR isoforms of localized transcripts are significantly longer than the 3' UTRs of non-localized transcripts and often code for proteins associated with axons, dendrites, and synapses. Surprisingly, long 3' UTRs add not only new, but also duplicate regulatory elements. The neuropil-enriched 3' UTR isoforms have significantly longer half-lives than somata-enriched isoforms. Finally, the 3' UTR isoforms can be significantly altered by enhanced activity. Most of the 3' UTR plasticity is transcription dependent, but intriguing examples of changes that are consistent with altered stability, trafficking between compartments, or local "remodeling" remain.
神经元将 mRNAs 定位在突触附近，其翻译可以通过突触需求和活动进行调节。mRNAs 的 3'UTR 的差异可以改变它们的定位、稳定性和翻译调控。通过对微切割大鼠脑片的 3'末端 RNA 测序，我们发现 mRNAs 的 3'UTR 存在巨大的多样性，许多转录物在胞体或神经突中表现出特定 3'UTR 亚型的富集。定位转录物的 3'UTR 亚型明显长于非定位转录物的 3'UTR，并且通常编码与轴突、树突和突触相关的蛋白质。令人惊讶的是，长的 3'UTR 不仅增加了新的，而且还增加了重复的调控元件。神经突富集的 3'UTR 亚型的半衰期明显长于胞体富集的亚型。最后，3'UTR 亚型可以通过增强的活性而显著改变。大多数 3'UTR 可塑性是转录依赖性的，但仍存在一些有趣的例子，表明存在与稳定性改变、细胞间运输或局部“重塑”一致的变化。
