Alvarez-Dominguez Juan R, Lodish Harvey F
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA.
Whitehead Institute for Biomedical Research, Cambridge, MA; and.
Blood. 2017 Nov 2;130(18):1965-1975. doi: 10.1182/blood-2017-06-788695. Epub 2017 Sep 19.
Long noncoding RNAs (lncRNAs) are increasingly recognized as vital components of gene programs controlling cell differentiation and function. Central to their functions is an ability to act as scaffolds or as decoys that recruit or sequester effector proteins from their DNA, RNA, or protein targets. lncRNA-modulated effectors include regulators of transcription, chromatin organization, RNA processing, and translation, such that lncRNAs can influence gene expression at multiple levels. Here we review the current understanding of how lncRNAs help coordinate gene expression to modulate cell fate in the hematopoietic system. We focus on a growing number of mechanistic studies to synthesize emerging principles of lncRNA function, emphasizing how they facilitate diversification of gene programming during development. We also survey how disrupted lncRNA function can contribute to malignant transformation, highlighting opportunities for therapeutic intervention in specific myeloid and lymphoid cancers. Finally, we discuss challenges and prospects for further elucidation of lncRNA mechanisms.
长链非编码RNA(lncRNAs)越来越被认为是控制细胞分化和功能的基因程序的重要组成部分。其功能的核心是能够作为支架或诱饵,从其DNA、RNA或蛋白质靶点招募或隔离效应蛋白。lncRNA调节的效应物包括转录、染色质组织、RNA加工和翻译的调节因子,因此lncRNAs可以在多个水平上影响基因表达。在这里,我们综述了目前对lncRNAs如何帮助协调基因表达以调节造血系统中细胞命运的理解。我们专注于越来越多的机制研究,以总结lncRNA功能的新出现的原则,强调它们如何在发育过程中促进基因编程的多样化。我们还调查了lncRNA功能紊乱如何导致恶性转化,突出了在特定髓系和淋巴系癌症中进行治疗干预的机会。最后,我们讨论了进一步阐明lncRNA机制的挑战和前景。