Begemann Gerrit
LS Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, Konstanz, Germany.
Zebrafish. 2008 Summer;5(2):111-9. doi: 10.1089/zeb.2008.0528.
Posttranscriptional regulation of gene activity has been a somewhat neglected subject in developmental genetics. With the discovery of RNA-mediated silencing mechanisms, however, insights into how targeted transcript inactivation integrates with developmental processes have changed radically. The number of studies in zebrafish that take advantage of techniques to manipulate the activity of microRNAs (miRNAs)--a group of short, noncoding RNAs that suppress translation of target genes--is on a steady rise, and the studies are starting to provide unique insights into the diversity of developmental processes that are controlled by transcript inhibition. Here I review recent studies in the zebrafish that demonstrate roles for miRNAs in the fine-tuning of neural crest cell migration, regulation of neural Hox gene expression, and regeneration after tissue amputation. New discoveries on the involvement of miRNAs in regulating red blood cell maturation also shed light on how miRNA gene activity itself is controlled. Because experimental suppression of single miRNAs often results in surprisingly specific phenotypes, it will have to be considered whether novel mutants identified in genetic screens should also be assayed for lesions in miRNA genes or their target sequences, rather than in protein-coding genes alone.
基因活性的转录后调控在发育遗传学中一直是一个有些被忽视的课题。然而,随着RNA介导的沉默机制的发现,对于靶向转录本失活如何与发育过程整合的认识发生了根本性的改变。利用技术操纵微小RNA(miRNA)——一组抑制靶基因翻译的短的非编码RNA——活性的斑马鱼研究数量正在稳步增加,这些研究开始为受转录抑制控制的发育过程的多样性提供独特的见解。在这里,我回顾了斑马鱼的近期研究,这些研究证明了miRNA在神经嵴细胞迁移的微调、神经Hox基因表达的调控以及组织截肢后的再生中的作用。关于miRNA参与调节红细胞成熟的新发现也揭示了miRNA基因活性本身是如何被控制的。由于对单个miRNA的实验性抑制常常导致惊人的特异性表型,因此必须考虑在遗传筛选中鉴定出的新突变体是否也应该检测miRNA基因或其靶序列中的损伤,而不仅仅是蛋白质编码基因中的损伤。