Dasgupta Ramanuj
New York University School of Medicine/Cancer Institute, Department of Pharmacology, New York, NY 10016, USA.
Curr Drug Targets. 2009 Jul;10(7):620-31. doi: 10.2174/138945009788680455.
The sequencing of whole genomes, including those of model organisms, has provided an unprecedented resource to the research community to make sense of the genetic code. However, it is the advent of novel functional genomic technologies that have been truly instrumental in bridging the gap between gene sequence and gene function. The past few years have witnessed a rapid growth in the development and implementation of high-throughput screening (HTS) technologies that researchers are now using to discover "gene-function" in an unbiased, systematic, time and cost-efficient manner. One of the most promising functional genomic approach that has emerged in the past few years is based on RNA-interference (RNAi) in which the introduction of double-stranded RNA (dsRNA) or short-interfering RNA (siRNA) into cells or whole organisms can effectively suppress endogenous gene expression. The RNAi-based screening technology has made it feasible to query the function of whole genomes in the regulation of conserved cell-signaling pathways and the crosstalk between them in "signaling networks" that are known to influence important cell biological functions, such as cell proliferation and growth, cell morphology, cell adhesion and cell death. In this review we discuss the application, advantages and limitations of RNAi and other post-genomic technologies in the identification of novel modulators of cell-signaling pathways, with a focus on the Wnt signaling pathway. We also discuss the future scope and utility of designing additional variants of these genome-scale screens.
全基因组测序，包括模式生物的基因组测序，为研究界提供了前所未有的资源，以解读遗传密码。然而，真正有助于弥合基因序列与基因功能之间差距的是新型功能基因组技术的出现。在过去几年中，高通量筛选（HTS）技术的开发和应用迅速发展，研究人员现在正使用这些技术以无偏见、系统、省时且经济高效的方式发现“基因功能”。过去几年中出现的最有前景的功能基因组方法之一是基于RNA干扰（RNAi），其中将双链RNA（dsRNA）或小干扰RNA（siRNA）引入细胞或整个生物体可以有效抑制内源性基因表达。基于RNAi的筛选技术使得在调控保守细胞信号通路及其在已知影响重要细胞生物学功能（如细胞增殖和生长、细胞形态、细胞黏附和细胞死亡）的“信号网络”中的相互作用方面查询全基因组功能成为可能。在本综述中，我们讨论RNAi和其他后基因组技术在鉴定细胞信号通路新型调节因子中的应用、优势和局限性，重点是Wnt信号通路。我们还讨论了设计这些基因组规模筛选的其他变体的未来范围和用途。
