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.
展开▼
机译：microRNA（miRNA）生物发生的第一步发生在细胞核中，并由包含RNase III样酶Drosha及其辅因子DGCR8的微处理器复合物介导。在这里，我们显示5'→3'核酸外切酶Xrn2与独立转录的miRNA缔合，并与Drosha加工结合，减弱了下游区域的转录。我们建议，在Drosha切割后，鱼雷样机制作用于新生的长前体miRNA，从而Xrn2核酸外切酶降解RNA聚合酶II相关的转录物，诱导其从模板中释放。尽管涉及初级转录终止，但这种减毒作用并不限制簇状miRNA的表达，在大多数情况下，簇状miRNA被短间隔子隔开。我们还显示，源自miRNA启动子的转录物保留在染色质模板上，并且比从mRNA或snRNA Pol II依赖性启动子产生的转录物更有效地加工。这些数据暗示转录和加工之间的偶联促进了独立转录的miRNA的有效表达。
展开▼
