Role of microRNAs in T cell development

RNA相互作用是真核生物蛋白质表达转录后调控的主要机制之一。这种机制是使用小的非编码RNA(MiRNAs)来破坏特定的mRNAs的稳定，并抑制蛋白质的合成。在胸腺发育过程中，许多miRNAs基因在T细胞中表达。然而，RNAi在T细胞发育中的作用仍不清楚。为了研究RNAi在胸腺发育中的作用，我们在小鼠中产生了对miRNA生成至关重要的DICER酶的条件敲除。我们观察到Dever缺陷小鼠的胸腺细胞数量急剧减少，我们确定其原因是胸腺细胞发育过程中从糖尿病肾病阶段到胸腺细胞发育DP阶段的进程受阻。重要的是，我们发现在RNAi缺陷的DP胸腺细胞中，促凋亡和抗凋亡因子之间的平衡发生了变化。我们还观察到RNAi缺陷的胸腺细胞正在迅速发生凋亡。最重要的是，我们还确定了确切的基因，其表达被microRNAs下调，以允许胸腺中发育中的T细胞存活。

RNA intererence is a one of the major mechanisms of post-transcriptional regulation of protein expression in eukaryotes. This mechanism is using small non-coding RNAs (miRNAs) to destabilize specific mRNAs and to suppress protein synthesis. Many miRNAs genes are expressed in T cells during development in a thymus. However the function of RNAi in T cell development remains unclear. To investigate the role of RNAi during thymic development we generated conditional knockout of the enzyme Dicer in the mouse, which is critical for miRNA generation. We observed a dramatic reduction in the number of thymocytes in Dicer-deficient mice and we determined that the reason is a block of progression from DN to DP stage during thymocyte development. Importantly, we found an alteration in the balance between pro- and anti-apoptotic factors in RNAi deficient DP thymocytes. We also observed that RNAi-deficient thymocytes are rapidly undergoing apoptosis. Most importantly, we have also identified the precise gene whose expression is downregulated by microRNAs to permit survival of developing T cells in the thymus.