Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
J Immunol. 2012 Apr 1;188(7):3257-67. doi: 10.4049/jimmunol.1103175. Epub 2012 Feb 29.
By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway is critical for the differentiation and function of T cells. Although 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 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 ∼168 kb. 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.
通过干扰 microRNA (miRNA) 的生物发生，我们之前已经表明该途径对 T 细胞的分化和功能至关重要。尽管各种克隆研究表明，许多 miRNA 在 T 细胞发育过程中以动态的方式表达，但不清楚这些早期分析的全面程度如何。因此，我们决定通过下一代测序来描绘 miRNA 的表达情况。此外，我们从造血干细胞开始描绘 miRNA 的表达情况。该分析表明，T 细胞发育过程中的 miRNA 表达极其动态，在测序的 645 个 miRNA 中，有些 miRNA 的表达变化幅度高达 3 个数量级。此外，前体加工的变化导致成熟 miRNA 序列发生改变。我们还分析了在 T 细胞中表达的初级 miRNA 转录物的结构，发现许多非常长。最长的是 pri-mir-29b-1/29a，约 168kb。所有的长 pri-miRNA 也都显示出广泛的剪接。我们的研究结果表明，T 细胞发育过程中的 miRNA 表达既是一个高度动态的过程，也是一个高度调节的过程。
