Molecular function and evolution of long non-coding RNA derived micro-peptides in normal neuronal differentiation

长链非编码rna （Long non-coding rna, lncRNAs）的长度约为100 ~ 200nt，被认为缺乏编码蛋白质的能力。它们在神经系统中富集，约40%的人类lncrna在大脑中特异性表达，具有精确的时空表达谱。长链非编码rna （lncRNAs）可以被翻译成非规范微肽，这一发现揭示了人类蛋白质组的一种未被探索的延伸。大多数这些微肽的功能尚未确定。这些特征具有重要的作用，特别是在膜和线粒体中。我们已经鉴定了一群从lncrna翻译而来的新型神经元微肽，它们是在神经元分化过程中产生的。本项目将剖析这些神经元微肽的分子功能，发现更多新的微肽，揭示这些lncRNA翻译事件的进化历史。新颖性和时效性：现在有强有力的证据表明lncrna衍生的微肽可以翻译，但分子机制对大多数人来说仍然是一个谜，尽管其中许多有助于细胞功能。在确定了lncrna中新的smorf的翻译之后，下一步令人兴奋的是了解这些微肽促进神经元分化的分子机制。我们最近还在灵长类动物中发现了36%的这些神经元微肽的潜在同源物。这为理解新型蛋白质编码基因从lncrna进化的机制提供了一个令人兴奋的基础。

Long non-coding RNAs (lncRNAs) are >200nt in length and were thought to lack the ability to encode proteins. They are enriched in the nervous system and ~40% of human lncRNAs are specifically expressed in the brain, with precise spatiotemporal expression profiles.The discovery that long non-coding RNAs (lncRNAs) can be translated to produce non-canonical micro-peptides has revealed an unexplored extension to the human proteome. The function of most of these micro-peptides have yet to be determined. Those that are characterised have important roles, particularly in membranes and mitochondria.We have identified a population of novel neuronal micro-peptides translated from lncRNAs, produced during neuronal differentiation. This project will dissect the molecular function of these neuronal micro-peptides, discover additional novel micro-peptides and reveal the evolutionary history of these lncRNA translation events.Novelty & timeliness: There is now robust evidence of translation lncRNA-derived micro-peptides, but molecular mechanisms still remain a mystery for the majority, though many contribute to cellular function. Having identified translation of novel smORFs within lncRNAs, the exciting next steps are to understand the molecular mechanisms by which these micro-peptides contribute to neuronal differentiation. We have also recently identified potential orthologs for 36% of these neuronal micro-peptides in primates. This provides an exciting basis from which to understand the mechanisms by which novel protein coding genes evolve from lncRNAs.