a State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences; Department of Obstetrics and Gynecology , Peking University Third Hospital, Peking University , Beijing , China.
b College of Life Sciences , Zhejiang Sci-Tech University , Hangzhou , China.
RNA Biol. 2018 Mar 4;15(3):413-422. doi: 10.1080/15476286.2018.1441665. Epub 2018 Mar 6.
Lineage-specific cell differentiation is a precise and coordinated biological process. To explore the roles of long noncoding RNA (lncRNA) in this process, the expression of polyA-minus RNAs was comparatively studied during the course of myocyte and adipocyte differentiation. In addition to identifying thousands of novel lncRNAs, distinct lncRNA profiles were revealed during lineage-specific differentiation, showing their active involvement in this process. This study further found that lncRNAs were organized in clusters and are co-regulated, constituting transcription open domains (TODs). In myocyte differentiation of C2C12 cells, loss-of-function screening identified three myogenic lncRNAs. Knockdown of their expression compromised not only the differentiation process, but also the essential signaling pathway. In addition to showing that lncRNAs are actively involved in cell differentiation, our results start to reveal a comprehensive signaling pathway, involving both protein and lncRNA factors.
谱系特异性细胞分化是一个精确而协调的生物学过程。为了探究长链非编码 RNA(lncRNA)在这一过程中的作用,本研究比较了肌细胞和脂肪细胞分化过程中多聚 A- 阴性 RNA 的表达。除了鉴定出数千种新的 lncRNA 外,在谱系特异性分化过程中还揭示了不同的 lncRNA 谱,表明它们积极参与这一过程。本研究进一步发现,lncRNA 以簇的形式组织,并受到共同调控,构成转录开放域(TODs)。在 C2C12 细胞的肌细胞分化中,功能丧失筛选鉴定出三个肌源性 lncRNA。这些 lncRNA 的表达缺失不仅损害了分化过程,还损害了必要的信号通路。除了表明 lncRNA 积极参与细胞分化外,我们的结果开始揭示一个全面的信号通路,涉及蛋白质和 lncRNA 因子。