Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
Neuron. 2015 Dec 2;88(5):861-877. doi: 10.1016/j.neuron.2015.09.045.
Only relatively recently has it become clear that mammalian genomes encode tens of thousands of long non-coding RNAs (lncRNAs). A striking 40% of these are expressed specifically in the brain, where they show precisely regulated temporal and spatial expression patterns. This begs the question, what is the functional role of these many lncRNA transcripts in the brain? Here we canvass a growing number of mechanistic studies that have elucidated central roles for lncRNAs in the regulation of nervous system development and function. We also survey studies indicating that neurological and psychiatric disorders may ensue when these mechanisms break down. Finally, we synthesize these insights with evidence from comparative genomics to argue that lncRNAs may have played important roles in brain evolution, by virtue of their abundant sequence innovation in mammals and plausible mechanistic connections to the adaptive processes that occurred recently in the primate and human lineages.
直到最近才清楚，哺乳动物基因组编码数万种长非编码 RNA（lncRNA）。其中，有惊人的 40%特异性地在大脑中表达，它们表现出精确调控的时空表达模式。这就提出了一个问题，这些大量的 lncRNA 转录本在大脑中的功能作用是什么？在这里，我们回顾了越来越多的机制研究，这些研究阐明了 lncRNA 在神经系统发育和功能调控中的核心作用。我们还调查了表明，当这些机制出现故障时，可能会导致神经和精神疾病。最后，我们综合这些见解和来自比较基因组学的证据，认为 lncRNA 可能通过其在哺乳动物中丰富的序列创新以及与最近在灵长类和人类谱系中发生的适应性过程的合理机制联系，在大脑进化中发挥了重要作用。
