Heme is involved in microRNA processing
Heme is involved in microRNA processing
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DOI：
10.1038/nsmb1182
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发表时间：
2007-01-01
影响因子：
16.8
通讯作者：
Guo, Feng
中科院分区：
文献类型：
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作者：
Faller, Michiel;Matsunaga, Michio;Guo, Feng
microRNAs（miRNAs）调控着大量蛋白质编码基因的表达。它们的初级转录物（pri-miRNAs）必须经历多个加工步骤才能达到功能形式。关于miRNAs的加工是如何被调节的知之甚少。在这里，我们表明，RNA结合蛋白DiGeorge关键区8（DGCR 8），这是必不可少的第一个加工步骤，是一个血红素结合蛋白。与血红素的缔合促进DGCR 8的二聚化。血红素结合的DGCR 8二聚体似乎在结合pri-miRNA时三聚化，并且在触发pri-miRNA切割中具有活性，而不含血红素的单体活性低得多。DGCR 8的血红素结合区抑制单体的pri-miRNA加工活性。这种假定的自抑制作用被血红素克服。我们发现血红素参与pri-miRNA的加工，这表明miRNA的基因调控网络和血红素参与的信号转导通路可能是相关的。
MicroRNAs ( miRNAs) regulate the expression of a large number of protein-coding genes. Their primary transcripts (pri-miRNAs) have to undergo multiple processing steps to reach the functional form. Little is known about how the processing of miRNAs is modulated. Here we show that the RNA-binding protein DiGeorge critical region-8 (DGCR8), which is essential for the first processing step, is a heme-binding protein. The association with heme promotes dimerization of DGCR8. The heme-bound DGCR8 dimer seems to trimerize upon binding pri-miRNAs and is active in triggering pri-miRNA cleavage, whereas the heme-free monomer is much less active. A heme-binding region of DGCR8 inhibits the pri-miRNA-processing activity of the monomer. This putative autoinhibition is overcome by heme. Our finding that heme is involved in pri-miRNA processing suggests that the gene-regulation network of miRNAs and signal-transduction pathways involving heme might be connected.