Integrative Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.
Immunol Rev. 2013 May;253(1):290-303. doi: 10.1111/imr.12048.
The discovery of microRNAs has renewed interest in posttranscriptional modes of regulation, fueling an emerging view of a rich RNA world within our cells that deserves further exploration. Much work has gone into elucidating genetic regulatory networks that orchestrate gene expression programs and direct cell fate decisions in the hematopoietic system. However, the focus has been to elucidate signaling pathways and transcriptional programs. To bring us one step closer to reverse engineering the molecular logic of cellular differentiation, it will be necessary to map posttranscriptional circuits as well and integrate them in the context of existing network models. In this regard, RNA-binding proteins (RBPs) may rival transcription factors as important regulators of cell fates and represent a tractable opportunity to connect the RNA world to the proteome. ChIP-seq has greatly facilitated genome-wide localization of DNA-binding proteins, helping us to understand genomic regulation at a systems level. Similarly, technological advances such as CLIP-seq allow transcriptome-wide mapping of RBP binding sites, aiding us to unravel posttranscriptional networks. Here, we review RBP-mediated posttranscriptional regulation, paying special attention to findings relevant to the immune system. As a prime example, we highlight the RBP Lin28B, which acts as a heterochronic switch between fetal and adult lymphopoiesis.
microRNAs 的发现重新激发了人们对转录后调控模式的兴趣，使人们对细胞内丰富的 RNA 世界产生了新的认识，值得进一步探索。人们已经做了大量工作来阐明遗传调控网络，这些网络协调着造血系统中基因表达程序和指导细胞命运的决定。然而，重点一直放在阐明信号通路和转录程序上。为了使我们更接近对细胞分化的分子逻辑进行逆向工程，有必要绘制转录后回路并将其整合到现有网络模型的背景中。在这方面，RNA 结合蛋白 (RBP) 可能与转录因子一样，成为细胞命运的重要调节剂，并为将 RNA 世界与蛋白质组联系起来提供了一个可行的机会。ChIP-seq 极大地促进了 DNA 结合蛋白的全基因组定位，帮助我们从系统水平上理解基因组调控。同样，CLIP-seq 等技术进步允许对 RBP 结合位点进行转录组范围的映射，帮助我们解开转录后网络。在这里，我们综述了 RBP 介导的转录后调控，特别关注与免疫系统相关的发现。作为一个主要的例子，我们强调了 RBP Lin28B，它在胎儿和成人淋巴生成之间起着异时性开关的作用。
