Ramos Alexander D, Attenello Frank J, Lim Daniel A
Department of Neurological Surgery, San Francisco, CA 94121, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA 94121, USA.
Department of Neurological Surgery, San Francisco, CA 94121, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA 94121, USA; San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Neurosci Lett. 2016 Jun 20;625:70-9. doi: 10.1016/j.neulet.2015.12.025. Epub 2015 Dec 28.
In the past decade, thousands of long noncoding RNAs (lncRNAs) have been identified, and emerging data indicate that lncRNAs can have important biological functions and roles in human diseases including cancer. Many lncRNAs appear to be expressed specifically in the brain, and the roles of lncRNAs in neural stem cells (NSCs) and brain development are now beginning to be discovered. Here we review recent advances in understanding the diversity of lncRNA structure and functions in NSCs and brain development. NSCs in the adult mouse ventricular-subventricular zone (V-SVZ) generate new neurons throughout life, and we discuss how key elements of this adult neurogenic system have facilitated the discovery and functional characterization of known and novel lncRNAs. A review of lncRNAs described in other NSC systems reveals a variety of molecular mechanisms, including binding and recruitment of transcription factors, epigenetic modifiers, and RNA-splicing factors. Finally, we review emerging evidence indicating that specific lncRNAs can be key drivers of glial tumors, and discuss next steps towards an in vivo understanding of lncRNA function in development and disease.
在过去十年中,已鉴定出数千种长链非编码RNA(lncRNA),新出现的数据表明lncRNA在包括癌症在内的人类疾病中可能具有重要的生物学功能和作用。许多lncRNA似乎在大脑中特异性表达,lncRNA在神经干细胞(NSC)和大脑发育中的作用目前才刚刚开始被发现。在此,我们综述了在理解NSC和大脑发育中lncRNA结构与功能多样性方面的最新进展。成年小鼠脑室下区(V-SVZ)中的NSC终生都能产生新的神经元,我们将讨论这个成体神经发生系统的关键要素如何促进了已知和新型lncRNA的发现及功能表征。对其他NSC系统中描述的lncRNA的综述揭示了多种分子机制,包括转录因子、表观遗传修饰因子和RNA剪接因子的结合与募集。最后,我们综述了新出现的证据,表明特定的lncRNA可能是胶质肿瘤的关键驱动因素,并讨论了在体内理解lncRNA在发育和疾病中的功能的下一步措施。