Current perspectives in intronic micro RNAs (miRNAs)
Current perspectives in intronic micro RNAs (miRNAs)
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DOI：
10.1007/s11373-005-9036-8
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发表时间：
2006-01-01
影响因子：
11
通讯作者：
Lin, SL
中科院分区：
文献类型：
--
作者：
Ying, SY;Lin, SL
微小RNA（miRNA）是一种能够干扰含有完全或部分互补性的细胞内信使RNA（mRNA）的小单链调节RNA，可用于设计针对癌症多态性和病毒突变的新疗法。已经报道了许多miRNA诱导RNA干扰（RNAi），一种转录后基因沉默机制。内含子miRNAs通过RNA剪接和Dicer加工从内含子衍生，可以干扰细胞内mRNA以沉默该基因的表达。内含子miRNA与先前描述的基因间miRNA的独特之处在于其生物发生需要II型RNA聚合酶（Pol-II）和剪接体组分。在秀丽隐杆线虫、小鼠和人类细胞中已经发现了几种内含子miRNAs，但其功能和应用尚未见报道。直到今天，计算机搜索miRNA的程序很少包括蛋白质编码RNA的内含子部分。人工产生的内含子miRNAs的功能意义已在几种生物系统如斑马鱼、鸡胚胎和成年小鼠中被成功地确定，表明这种基因调控系统在体内的进化保存。多个miRNA可以从相同的内含子簇产生;然而，非同源的miRNA可以具有不同的靶标和功能，而同源的miRNA可以源自不同的内含子簇。总之，内含子miRNA介导的转基因动物模型提供了一种研究体内miRNA相关疾病机制的工具，并将为miRNA相关治疗提供启示。
MicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering with intracellular messenger RNAs (mRNAs) that contain either complete or partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. Numerous miRNAs have been reported to induce RNA interference (RNAi), a post-transcriptional gene silencing mechanism. Intronic miRNAs, derived from introns by RNA splicing and Dicer processing, can interfere with intracellular mRNAs to silence that gene expression. The intronic miRNAs differ uniquely from previously described intergenic miRNAs in the requirement of type II RNA polymerases (Pol-II) and spliceosomal components for its biogenesis. Several kinds of intronic miRNAs have been identified in Caenorhabditis elegans, mouse and human cells; however, neither their function nor application has been reported. To this day, the computer searching program for miRNA seldom include the intronic portion of protein-coding RNAs. The functional significance of artificially generated intronic miRNAs has been successfully ascertained in several biological systems such as zebrafishes, chicken embryos and adult mice, indicating the evolutionary preservation of this gene regulation system in vivo. Multiple miRNAs can be generated from the same cluster of introns; however, non-homologous miRNAs may have different targets and functions while homologous miRNA may be derived from different intronic clusters. Taken together, the model of intronic miRNA-mediated transgenic animals provides a tool to investigate the mechanism of miRNA-associated diseases in vivo and will shed light on miRNA-related therapies.