Arndt G M, Rank G H
Department of Biology, University of Saskatchewan, Saskatoon, Canada.
Genome. 1997 Dec;40(6):785-97. doi: 10.1139/g97-802.
The use of complementary RNA sequences such as antisense RNAs and ribozymes to regulate the expression of specific genes in eukaryotic cells has been well-documented, particularly with their application to both human gene therapy and plant biotechnology. Despite the simplicity of this approach, this technique usually results in only partial suppression of gene expression and, in some instances, even fails to regulate the gene of interest. The variation observed with antisense RNA and ribozyme-mediated regulation is further complicated by the many factors with the potential to impact on the effectiveness of these RNAs. Recent advances in the understanding of the global architecture of the nucleus, chromatin structure, and RNA metabolism provide useful and necessary information for designing novel approaches to improving antisense RNA and ribozyme regulation. These studies predict that the position of genes within the nucleus is not random and that transcripts produced from these genes follow specific tracks in migrating to the cell cytoplasm. These observations have the potential to impact significantly on the ways in which RNA-mediated forms of gene regulation are applied. The purpose of this review is to discuss the concept of colocalizing antisense RNAs and ribozymes with their target mRNAs and to introduce a variety of approaches aimed at achieving this goal.
利用互补RNA序列（如反义RNA和核酶）来调控真核细胞中特定基因的表达，这一点已有充分记录，尤其是在其应用于人类基因治疗和植物生物技术方面。尽管这种方法很简单，但该技术通常只会导致基因表达的部分抑制，在某些情况下，甚至无法调控目标基因。反义RNA和核酶介导的调控中观察到的变化，因许多可能影响这些RNA有效性的因素而进一步复杂化。对细胞核的整体结构、染色质结构和RNA代谢的最新认识进展，为设计改进反义RNA和核酶调控的新方法提供了有用且必要的信息。这些研究预测，基因在细胞核内的位置并非随机，并且从这些基因产生的转录本在迁移到细胞质的过程中遵循特定轨迹。这些观察结果可能会对RNA介导的基因调控形式的应用方式产生重大影响。本综述的目的是讨论将反义RNA和核酶与其靶标mRNA共定位的概念，并介绍旨在实现这一目标的各种方法。
