Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), I-90128 Palermo, Italy.
Department of Experimental Biomedicine and Clinical Neurosciences (BIONEC), University of Palermo, I-90127 Palermo, Italy.
Int J Mol Med. 2014 Apr;33(4):747-62. doi: 10.3892/ijmm.2014.1629. Epub 2014 Jan 21.
Post-transcriptional control of mRNA trafficking and metabolism plays a critical role in the actualization and fine tuning of the genetic program of cells, both in development and in differentiated tissues. Cis-acting signals, responsible for post-transcriptional regulation, reside in the RNA message itself, usually in untranslated regions, 5' or 3' to the coding sequence, and are recognized by trans-acting factors: RNA-binding proteins (RBPs) and/or non-coding RNAs (ncRNAs). ncRNAs bind short mRNA sequences usually present in the 3'-untranslated (3'-UTR) region of their target messages. RBPs recognize specific nucleotide sequences and/or secondary/tertiary structures. Most RBPs assemble on mRNA at the moment of transcription and shepherd it to its destination, somehow determining its final fate. Regulation of mRNA localization and metabolism has a particularly important role in the nervous system where local translation of pre-localized mRNAs has been implicated in developing axon and dendrite pathfinding, and in synapse formation. Moreover, activity-dependent mRNA trafficking and local translation may underlie long-lasting changes in synaptic efficacy, responsible for learning and memory. This review focuses on the role of RBPs in neuronal development and plasticity, as well as possible connections between ncRNAs and RBPs.
mRNA 转译后调控对细胞基因程序的实现和微调起着至关重要的作用,无论是在发育过程中还是在分化组织中都是如此。顺式作用信号负责转录后调控,位于 RNA 信息本身中,通常在编码序列的 5' 或 3' 非翻译区,并被反式作用因子识别:RNA 结合蛋白 (RBPs) 和/或非编码 RNA (ncRNAs)。ncRNAs 结合其靶信使中通常存在于 3' 非翻译区 (3'-UTR) 的短 mRNA 序列。RBPs 识别特定的核苷酸序列和/或二级/三级结构。大多数 RBP 在转录时与 mRNA 组装,并引导其到达目的地,在某种程度上决定其最终命运。mRNA 定位和代谢的调节在神经系统中具有特别重要的作用,其中局部翻译预先定位的 mRNAs 已被牵连到轴突和树突寻路以及突触形成中。此外,与活动相关的 mRNA 运输和局部翻译可能是突触效能的长期变化的基础,而突触效能的长期变化与学习和记忆有关。本综述重点介绍 RBPs 在神经元发育和可塑性中的作用,以及 ncRNAs 和 RBPs 之间可能存在的联系。