Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome.

Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome.
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上斜肌组中MRNA剪接和microRNA生物发生之间的相互作用。

DOI:
10.1093/nar/gkt1413
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发表时间:
2014-04
影响因子:
14.9
通讯作者:
Sperling R
Sperling R
中科院分区:
生物学2区
文献类型:
--
作者:
Agranat-Tamir L;Shomron N;Sperling J;Sperling R

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MicroRNA (miRNA) 是基因表达的中央调节因子,其中很大一部分是在 RNA 聚合酶 II 转录本的内含子中编码的。因此,微处理器对内含子 miRNA 的生物合成以及剪接体对宿主内含子的剪接需要这些处理事件之间的协调。这里解决了这种串扰。我们展示了关键的微处理器蛋白 Drosha 和 DGCR8 以及 pre-miRNA 与执行核转录后处理的上剪接体共沉积。我们进一步表明,剪接的抑制会增加 miRNA 的表达,而 Drosha 的敲除会增加剪接。我们在 MCM7 的内含子 13(miR-106b-25 簇所在的位置)中发现了一个新的剪接事件。独特的剪接亚型包括延伸外显子中的托管前 miRNA,并排除其加工。这表明了改变源自同一转录本的不同 miRNA 水平的可能机制。总而言之,我们的研究表明在超剪接体背景下剪接和微处理器机器之间的相互作用。
MicroRNAs (miRNAs) are central regulators of gene expression, and a large fraction of them are encoded in introns of RNA polymerase II transcripts. Thus, the biogenesis of intronic miRNAs by the microprocessor and the splicing of their host introns by the spliceosome require coordination between these processing events. This cross-talk is addressed here. We show that key microprocessor proteins Drosha and DGCR8 as well as pre-miRNAs cosediment with supraspliceosomes, where nuclear posttranscriptional processing is executed. We further show that inhibition of splicing increases miRNAs expression, whereas knock-down of Drosha increases splicing. We identified a novel splicing event in intron 13 of MCM7, where the miR-106b-25 cluster is located. The unique splice isoform includes a hosted pre-miRNA in the extended exon and excludes its processing. This indicates a possible mechanism of altering the levels of different miRNAs originating from the same transcript. Altogether, our study indicates interplay between the splicing and microprocessor machineries within a supraspliceosome context.
在含microRNA的内含子处的前馈微孔处理和剪接活性。
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