AGO2直接结合tRNA基因并顺式促进基因抑制。
Argonaute 2 Binds Directly to tRNA Genes and Promotes Gene Repression in cis.
作者信息
Woolnough Jessica L, Atwood Blake L, Giles Keith E
出版信息
Mol Cell Biol. 2015 Jul;35(13):2278-94. doi: 10.1128/MCB.00076-15.
Abstract
To further our understanding of the RNAi machinery within the human nucleus, we analyzed the chromatin and RNA binding of Argonaute 2 (AGO2) within human cancer cell lines. Our data indicated that AGO2 binds directly to nascent tRNA and 5S rRNA, and to the genomic loci from which these RNAs are transcribed, in a small RNA- and DICER-independent manner. AGO2 chromatin binding was not observed at non-TFIIIC-dependent RNA polymerase III (Pol III) genes or at extra-TFIIIC (ETC) sites, indicating that the interaction is specific for TFIIIC-dependent Pol III genes. A genome-wide analysis indicated that loss of AGO2 caused a global increase in mRNA expression level among genes that flank AGO2-bound tRNA genes. This effect was shown to be distinct from that of the disruption of DICER, DROSHA, or CTCF. We propose that AGO2 binding to tRNA genes has a novel and important regulatory role in human cells.
摘要
为了进一步了解人类细胞核内的RNA干扰机制，我们分析了人类癌细胞系中AGO2（Argonaute 2）的染色质和RNA结合情况。我们的数据表明，AGO2以一种不依赖小RNA和DICER的方式直接结合新生tRNA和5S rRNA，以及这些RNA转录的基因组位点。在非TFIIIC依赖的RNA聚合酶III（Pol III）基因或TFIIIC外（ETC）位点未观察到AGO2染色质结合，这表明这种相互作用对TFIIIC依赖的Pol III基因具有特异性。全基因组分析表明，AGO2缺失导致AGO2结合的tRNA基因侧翼基因的mRNA表达水平整体上升。这种效应与DICER、DROSHA或CTCF的破坏所产生的效应不同。我们提出，AGO2与tRNA基因的结合在人类细胞中具有新的重要调节作用。
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