Coupled RNA Processing and Transcription of Intergenic Primary MicroRNAs
Coupled RNA Processing and Transcription of Intergenic Primary MicroRNAs
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DOI：
10.1128/mcb.00664-09
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发表时间：
2009-10-15
影响因子：
5.3
通讯作者：
Bozzoni, Irene
中科院分区：
文献类型：
--
作者：
Ballarino, Monica;Pagano, Francesca;Bozzoni, Irene
MicroRNA(MiRNA)生物发生的第一步发生在细胞核中，由含有RNaseIII样酶DROSHA及其辅因子Dgcr8的微处理器复合体介导。在这里，我们证明了5‘->；3’外切酶Xrn2与独立转录的miRNAs相关，并与DROSHA处理结合，减弱了下游区域的转录。我们认为，在DROSHA切割后，一种类似鱼雷的机制作用于新生的长前体miRNAs，借此Xrn2外切酶降解RNA聚合酶II相关的转录物，导致其从模板中释放。虽然参与初级转录终止，但这种衰减效应并不限制成簇的miRNA表达，在大多数情况下，成簇的miRNA由短间隔子分隔。我们还表明，来自miRNA启动子的转录本被保留在染色质模板上，并且比那些来自mRNA或SnRNA Pol II依赖的启动子产生的转录本更有效地处理。这些数据表明，转录和处理之间的耦合促进了独立转录的miRNAs的有效表达。
The first step in microRNA (miRNA) biogenesis occurs in the nucleus and is mediated by the Microprocessor complex containing the RNase III-like enzyme Drosha and its cofactor DGCR8. Here we show that the 5'-->3' exonuclease Xrn2 associates with independently transcribed miRNAs and, in combination with Drosha processing, attenuates transcription in downstream regions. We suggest that, after Drosha cleavage, a torpedo-like mechanism acts on nascent long precursor miRNAs, whereby Xrn2 exonuclease degrades the RNA polymerase II-associated transcripts inducing its release from the template. While involved in primary transcript termination, this attenuation effect does not restrict clustered miRNA expression, which, in the majority of cases, is separated by short spacers. We also show that transcripts originating from a miRNA promoter are retained on the chromatin template and are more efficiently processed than those produced from mRNA or snRNA Pol II-dependent promoters. These data imply that coupling between transcription and processing promotes efficient expression of independently transcribed miRNAs.