Dynamic microRNA gene transcription and processing during T cell development.
Dynamic microRNA gene transcription and processing during T cell development.
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DOI：
10.4049/jimmunol.1103175
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
Chong MM
中科院分区：
文献类型：
--
作者：
Kirigin FF;Lindstedt K;Sellars M;Ciofani M;Low SL;Jones L;Bell F;Pauli F;Bonneau R;Myers RM;Littman DR;Chong MM
通过干扰微小RNA（miRNA）的生物发生过程，我们之前表明该途径对T细胞的分化和功能至关重要。虽然各种克隆研究表明许多miRNA在T细胞发育过程中以动态方式表达，但不清楚这些早期分析有多全面。因此，我们决定通过新一代测序来分析miRNA的表达。此外，我们从造血干细胞开始分析miRNA的表达。该分析显示，T细胞发育过程中的miRNA表达极具动态性，共对645种miRNA进行了测序，有些miRNA的表达量变化高达3个数量级。此外，前体加工的变化导致成熟miRNA序列改变。我们还分析了在T细胞中表达的初级miRNA转录本的结构，发现许多都非常长。最长的是pri - mir - 29b - 1/29a，约168kb。所有长的初级miRNA也都表现出广泛的剪接。我们的研究结果表明，T细胞发育过程中的miRNA表达是一个高度动态且受到高度调控的过程。
By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway is critical for the differentiation and function of T cells. While various cloning studies have shown that many miRNAs are expressed during T cell development, and in a dynamic manner, it was unclear how comprehensive these earlier analyses were. We therefore decided to profile miRNA expression by means of Next Generation Sequencing. Furthermore, we profiled miRNA expression starting from the hematopoietic stem cell. This analysis revealed that miRNA expression during T cell development is extremely dynamic, with 645 miRNAs sequenced, and the expression of some varying by as much as 3 orders of magnitude. Furthermore, changes in precursor processing led to altered mature miRNA sequences. We also analyzed the structures of the primary miRNA transcripts expressed in T cells, and found that many were extremely long. The longest was pri-mir-29b-1/29a at ~168kb. All the long pri-miRNAs also displayed extensive splicing. Our findings indicate that miRNA expression during T cell development is both a highly dynamic and a highly regulated process.
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