Sevignani Cinzia, Calin George A, Siracusa Linda D, Croce Carlo M
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
Mamm Genome. 2006 Mar;17(3):189-202. doi: 10.1007/s00335-005-0066-3. Epub 2006 Mar 3.
The basis of eukaryotic complexity is an intricate genetic architecture where parallel systems are involved in tuning gene expression, via RNA-DNA, RNA-RNA, RNA-protein, and DNA-protein interactions. In higher organisms, about 97% of the transcriptional output is represented by noncoding RNA (ncRNA) encompassing not only rRNA, tRNA, introns, 5' and 3' untranslated regions, transposable elements, and intergenic regions, but also a large, rapidly emerging family named microRNAs. MicroRNAs are short 20-22-nucleotide RNA molecules that have been shown to regulate the expression of other genes in a variety of eukaryotic systems. MicroRNAs are formed from larger transcripts that fold to produce hairpin structures and serve as substrates for the cytoplasmic Dicer, a member of the RNase III enzyme family. A recent analysis of the genomic location of human microRNA genes suggested that 50% of microRNA genes are located in cancer-associated genomic regions or in fragile sites. This review focuses on the possible implications of microRNAs in post-transcriptional gene regulation in mammalian diseases, with particular focus on cancer. We argue that developing mouse models for deleted and/or overexpressed microRNAs will be of invaluable interest to decipher the regulatory networks where microRNAs are involved.
真核生物复杂性的基础是一种复杂的遗传结构，其中并行系统通过RNA-DNA、RNA-RNA、RNA-蛋白质和DNA-蛋白质相互作用参与调节基因表达。在高等生物中，约97%的转录产物由非编码RNA（ncRNA）代表，其不仅包括rRNA、tRNA、内含子、5'和3'非翻译区、转座元件和基因间区域，还包括一个庞大且迅速兴起的名为微小RNA的家族。微小RNA是短的20-22个核苷酸的RNA分子，已被证明在多种真核系统中调节其他基因的表达。微小RNA由较大的转录本形成，这些转录本折叠产生发夹结构，并作为细胞质Dicer（RNase III酶家族的成员）的底物。最近对人类微小RNA基因基因组位置的分析表明，50%的微小RNA基因位于与癌症相关的基因组区域或脆性位点。本综述重点关注微小RNA在哺乳动物疾病转录后基因调控中的可能影响，尤其关注癌症。我们认为，开发缺失和/或过表达微小RNA的小鼠模型对于破译微小RNA所涉及的调控网络将具有极其重要的意义。
