Role of microRNAs in T cell development

RNA干扰是转录后调控的主要机制之一， 真核生物中的蛋白质表达。这种机制是利用小的非编码RNA（miRNA）， 使特定mRNA不稳定并抑制蛋白质合成。许多miRNAs基因表达 在胸腺发育过程中的T细胞。然而，RNAi在T细胞发育中的功能 仍不清楚为了研究RNAi在胸腺发育过程中的作用，我们产生了 在小鼠中条件性敲除酶Dicer，这对miRNA的产生至关重要。 我们观察到Dicer缺陷小鼠的胸腺细胞数量显著减少， 确定其原因是胸腺细胞从DN到DP阶段的进展受阻， 发展重要的是，我们发现了亲， RNAi缺陷型DP胸腺细胞中的抗凋亡因子。我们还观察到， 胸腺细胞正在迅速经历凋亡。最重要的是，我们还确定了 一种精确的基因，其表达被microRNA下调，以允许发育中的T细胞存活 胸腺细胞因为Let7家族是最大的miRNA家族，我们有 现在研究Let7家族microRNA在胸腺T细胞发育中的作用。我们发现 Let7 miRNAs靶向转录因子PLZF，从而调节细胞的分化， 胸腺中的先天性T细胞（即NKT细胞）。

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. Because the Let7 family of microRNAs is the largest miRNA family, we have now examined the role of Let7 family microRNAs in T cell development in the thymus. We found that Let7 miRNAs target the transcription factor PLZF and so regulate the differentiation of innate-like T cells (i.e. NKT cells) in the thymus.