Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel, Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel and Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Nucleic Acids Res. 2014 Apr;42(7):4640-51. doi: 10.1093/nar/gkt1413. Epub 2014 Jan 24.
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.
微小 RNA（miRNAs）是基因表达的核心调控因子，其中很大一部分是 RNA 聚合酶 II 转录本内含子编码的。因此，内含子 miRNA 的微处理器生物发生和它们的宿主内含子的剪接体剪接需要这些加工事件之间的协调。本文探讨了这种串扰。我们表明，关键的微处理器蛋白 Drosha 和 DGCR8 以及前 miRNA 与核转录后加工执行的超剪接体共沉淀。我们进一步表明，剪接抑制会增加 miRNA 的表达，而 Drosha 的敲低会增加剪接。我们在 MCM7 的内含子 13 中鉴定出一种新的剪接事件，miR-106b-25 簇就位于此处。独特的剪接异构体在扩展的外显子中包含一个被宿主的前 miRNA，并排除其加工。这表明了一种可能的机制，可以改变来自同一转录本的不同 miRNA 的水平。总之，我们的研究表明，在超剪接体环境中，剪接和微处理器机制之间存在相互作用。
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