Science:曹雪涛解析人类树突状细胞分化的非编码RNA机制

2014-04-19 koo 生物360

日前,来自第二军医大学、中国医学科学院和浙江大学医学院的研究人员,发现一种名为 lnc-DC 的长链非编码 RNA 控制了人类树突状细胞的分化。这些重要的研究结果在线发表在4月18日的《科学》(Science)杂志上。领导这一研究的是我国著名的免疫学家曹雪涛(Xuetao Cao)院士。 长链非编码 RNA(lncRNA)是一类转录本长度超过 200nt 的 RNA 分子,起初研

日前,来自第二军医大学、中国医学科学院和浙江大学医学院的研究人员,发现一种名为 lnc-DC 的长链非编码 RNA 控制了人类树突状细胞的分化。这些重要的研究结果在线发表在4月18日的《科学》(Science)杂志上。领导这一研究的是我国著名的免疫学家曹雪涛(Xuetao Cao)院士。




长链非编码 RNA(lncRNA)是一类转录本长度超过 200nt 的 RNA 分子,起初研究人员发现它们并不编码蛋白,因此将它们认作为是基因组转录的“噪音”,不具有生物学功能。然而,近年来的研究发现, lncRNA 参与调控了机体的生长发育、细胞凋亡、增殖、分化等,与多种疾病密切相关。但到目前为止还只报道了少数调控免疫系统的 lncRNAs 。

树突状细胞(DCs)是哺乳动物免疫系统中最有力的抗原递呈细胞;它们的分化和功能对先天免疫和适应性免疫应答具有重要的影响。尽管已经确定了一些转录因子和细胞因子在DC细胞群的生成与稳态中发挥至关重要的作用,对于在 DC 分化和功能中起作用的非编码 RNA ,尤其是 lncRNAs 仍然知之甚少。

不同于 microRNA 已经确立的作用机制:是基于种子序列互补配对,对于 lncRNAs 的作用机制仍未充分理解。少数的 lncRNAs 是通过与细胞核中的异核蛋白或染色质修饰复合体相互作用来发挥功能,而另一些则是通过影响细胞质中的 mRNA 稳定或转录。目前尚不清楚是否还存在其他未知的 lncRNAs 作用模式。

在这篇新论文中,研究人员利用广泛接受的、诱导外周血单核细胞分化为人类树突状细胞的模型,进行转录组微阵列分析和 RNA 测序,鉴别出了唯独表达于人类 DCs 中的一种长链非编码 RNA: lnc-DC 。他们证实抑制 lnc-DC 可破坏体外人类外周血单核细胞以及体内的小鼠骨髓细胞分化为 DC,并减小了 DCs 刺激T细胞激活的能力。

进一步的机制研究证实, lnc-DC 是通过激活转录因子 STAT3 来介导这些效应的。 lnc-DC 直接结合到细胞质中的 STAT3 上,通过阻止 STAT3 结合 SHP1 及被去磷酸化,促进了 STAT3 tyrosine-705 位点磷酸化。

新研究确定了一个调控 DC 分化的 lncRNA ,并扩宽了已知的 lncRNA 作用机制。

原始出处:

Pin Wang, Yiquan Xue, Yanmei Han, Li Lin, Cong Wu, Sheng Xu, Zhengping Jiang, Junfang Xu,Qiuyan Liu, and Xuetao Cao. The STAT3-Binding Long Noncoding RNA lnc-DC Controls Human Dendritic Cell Differentiation. Science, 18 April 2014; DOI:10.1126/science.1251456

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    2015-03-27 hongbochen
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    2014-11-20 d830384
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    2014-04-21 jichang
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