C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts.

C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts.
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DOI:
10.1093/nar/gkp205
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发表时间:
2009-06
影响因子:
14.9
通讯作者:
Cavaillé J
Cavaillé J
中科院分区:
生物学2区
文献类型:
--
作者:
Bortolin-Cavaillé ML;Dance M;Weber M;Cavaillé J

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MicroRNAs是一种微小的RNA分子,在广泛的发育、生理或病理过程中发挥着重要的调节作用。尽管最近我们在了解miRNA的加工和生物学功能方面取得了进展,但对在转录水平上控制其表达的调控机制知之甚少。C19MC是迄今为止发现的最大的人类microRNA基因簇。这个100kb长的簇由46个重复的灵长类动物特异的前∼基因组成,这些基因两侧有AlU元件(ALU),并嵌入到一个400到700个核苷酸长的重复单元中。有研究认为,C19MC miRNA基因是由RNA聚合酶III(Pol-III)转录的,该基因起始于A和B盒,嵌入上游Alu重复序列。在这里,我们发现C19MC miRNAs是由Dgcr8-DROSHA(微处理器)复合体内含子编码的,并由Dgcr8-DROSHA(微处理器)复合体处理,该转录本来自先前未知的、非蛋白质编码的Pol-II(而不是Pol-III)转录本,该转录本主要在胎盘中表达,如果不是唯一的话。
MicroRNAs are tiny RNA molecules that play important regulatory roles in a broad range of developmental, physiological or pathological processes. Despite recent progress in our understanding of miRNA processing and biological functions, little is known about the regulatory mechanisms that control their expression at the transcriptional level. C19MC is the largest human microRNA gene cluster discovered to date. This 100-kb long cluster consists of 46 tandemly repeated, primate-specific pre-miRNA genes that are flanked by Alu elements (Alus) and embedded within a ∼400- to 700-nt long repeated unit. It has been proposed that C19MC miRNA genes are transcribed by RNA polymerase III (Pol-III) initiating from A and B boxes embedded in upstream Alu repeats. Here, we show that C19MC miRNAs are intron-encoded and processed by the DGCR8-Drosha (Microprocessor) complex from a previously unidentified, non-protein-coding Pol-II (and not Pol-III) transcript which is mainly, if not exclusively, expressed in the placenta.
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