Department of Neurological Surgery, University of California, San Francisco, Ray and Dagmar Dolby Regeneration Medicine Building, 35 Medical Center Way, RMB 1037, San Francisco, CA, 94143, USA.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, 94143, USA.
Cell Tissue Res. 2018 Jan;371(1):55-71. doi: 10.1007/s00441-017-2711-z. Epub 2017 Oct 27.
During both development and adulthood, the human brain expresses many thousands of long noncoding RNAs (lncRNAs), and aberrant lncRNA expression has been associated with a wide range of neurological diseases. Although the biological significance of most lncRNAs remains to be discovered, it is now clear that certain lncRNAs carry out important functions in neurodevelopment, neural cell function, and perhaps even diseases of the human brain. Given the relatively inclusive definition of lncRNAs-transcripts longer than 200 nucleotides with essentially no protein coding potential-this class of noncoding transcript is both large and very diverse. Furthermore, emerging data indicate that lncRNA genes can act via multiple, non-mutually exclusive molecular mechanisms, and specific functions are difficult to predict from lncRNA expression or sequence alone. Thus, the different experimental approaches used to explore the role of a lncRNA might each shed light upon distinct facets of its overall molecular mechanism, and combining multiple approaches may be necessary to fully illuminate the function of any particular lncRNA. To understand how lncRNAs affect brain development and neurological disease, in vivo studies of lncRNA function are required. Thus, in this review, we focus our discussion upon a small set of neural lncRNAs that have been experimentally manipulated in mice. Together, these examples illustrate how studies of individual lncRNAs using multiple experimental approaches can help reveal the richness and complexity of lncRNA function in both neurodevelopment and diseases of the brain.
在人类的发育和成年期，大脑表达了成千上万种长链非编码 RNA（lncRNA），异常的 lncRNA 表达与广泛的神经疾病有关。尽管大多数 lncRNA 的生物学意义仍有待发现，但现在清楚的是，某些 lncRNA 在神经发育、神经细胞功能中发挥着重要作用，甚至在人类大脑疾病中也发挥着重要作用。鉴于 lncRNA 的定义相对广泛——转录本长度超过 200 个核苷酸，几乎没有蛋白质编码潜力——这一类非编码转录本不仅数量庞大，而且非常多样化。此外，新出现的数据表明，lncRNA 基因可以通过多种非互斥的分子机制发挥作用，特定的功能很难仅从 lncRNA 的表达或序列来预测。因此，用于探索 lncRNA 作用的不同实验方法可能各自揭示其整体分子机制的不同方面，并且可能需要结合多种方法才能充分阐明任何特定 lncRNA 的功能。为了了解 lncRNA 如何影响大脑发育和神经疾病，需要对 lncRNA 的功能进行体内研究。因此，在这篇综述中，我们将重点讨论一小部分已经在小鼠中进行了实验操作的神经 lncRNA。这些例子共同说明了如何使用多种实验方法研究单个 lncRNA，以帮助揭示 lncRNA 在神经发育和大脑疾病中的丰富和复杂性。
