环状RNA在造血和血液系统恶性肿瘤中的作用
CircRNAs in hematopoiesis and hematological malignancies
原文发布日期:2016-10-14
DOI: 10.1038/bcj.2016.81
类型: Review
开放获取: 是
英文摘要:
摘要翻译:
原文链接:
Cell states in hematopoiesis are controlled by master regulators and by complex circuits of a growing family of RNA species impacting cell phenotype maintenance and plasticity. Circular RNAs (circRNAs) are rapidly gaining the status of particularly stable transcriptome members with distinctive qualities. RNA-seq identified thousands of circRNAs with developmental stage- and tissue-specific expression corroborating earlier suggestions that circular isoforms are a natural feature of the cell expression program. CircRNAs are abundantly expressed also in the hematopoietic compartment. There are a number of studies on circRNAs in blood cells, a specific overview is however lacking. In this review we first present current insight in circRNA biogenesis discussing the relevance for hematopoiesis of the highly interleaved processes of splicing and circRNA biogenesis. Regarding molecular functions circRNAs modulate host gene expression, but also compete for binding of microRNAs, RNA-binding proteins or translation initiation and participate in regulatory circuits. We examine circRNA expression in the hematopoietic compartment and in hematologic malignancies and review the recent breakthrough study that identified pathogenic circRNAs derived from leukemia fusion genes. CircRNA high and regulated expression in blood cell types indicate that further studies are warranted to inform the position of these regulators in normal and malignant hematopoiesis.
造血过程中的细胞状态受主调控因子及日益增多的RNA家族复杂环路所控制,这些RNA影响着细胞表型的维持与可塑性。环状RNA(circRNAs)正迅速成为具有独特性质的特别稳定的转录组成员。RNA测序技术已识别出数千种具有发育阶段和组织特异性表达的环状RNA,这证实了早期观点:环状异构体是细胞表达程序的自然特征。环状RNA在造血系统中亦大量表达。目前已有大量关于血细胞中环状RNA的研究,但尚缺乏系统性综述。本文首先阐述了当前对环状RNA生物发生的认知,探讨了剪接与环状RNA生物发生高度交织过程对造血的意义。在分子功能层面,环状RNA不仅能调控宿主基因表达,还可竞争性结合微小RNA、RNA结合蛋白或翻译起始因子,并参与调控网络。我们分析了环状RNA在造血系统及血液恶性肿瘤中的表达,并综述了近期突破性研究——这些研究发现了源自白血病融合基因的致病性环状RNA。环状RNA在血细胞类型中的高表达及调控性表达表明,需要进一步研究以明确这些调控因子在正常与恶性造血过程中的作用地位。
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