Mattick J S
ARC Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia.
EMBO Rep. 2001 Nov;2(11):986-91. doi: 10.1093/embo-reports/kve230.
Around 98% of all transcriptional output in humans is non-coding RNA. RNA-mediated gene regulation is widespread in higher eukaryotes and complex genetic phenomena like RNA interference, co-suppression, transgene silencing, imprinting, methylation, and possibly position-effect variegation and transvection, all involve intersecting pathways based on or connected to RNA signaling. I suggest that the central dogma is incomplete, and that intronic and other non-coding RNAs have evolved to comprise a second tier of gene expression in eukaryotes, which enables the integration and networking of complex suites of gene activity. Although proteins are the fundamental effectors of cellular function, the basis of eukaryotic complexity and phenotypic variation may lie primarily in a control architecture composed of a highly parallel system of trans-acting RNAs that relay state information required for the coordination and modulation of gene expression, via chromatin remodeling, RNA-DNA, RNA-RNA and RNA-protein interactions. This system has interesting and perhaps informative analogies with small world networks and dataflow computing.
人类所有转录产物中约98%是非编码RNA。RNA介导的基因调控在高等真核生物中广泛存在,诸如RNA干扰、共抑制、转基因沉默、印记、甲基化等复杂的遗传现象,可能还有位置效应斑驳和异位显性,都涉及基于或与RNA信号传导相关的交叉途径。我认为中心法则并不完整,内含子和其他非编码RNA已经进化为真核生物基因表达的第二层,这使得复杂的基因活动套件能够整合和联网。虽然蛋白质是细胞功能的基本效应器,但真核生物复杂性和表型变异的基础可能主要在于一个由反式作用RNA高度并行系统组成的控制架构,该系统通过染色质重塑、RNA-DNA、RNA-RNA和RNA-蛋白质相互作用传递基因表达协调和调节所需的状态信息。这个系统与小世界网络和数据流计算有有趣且可能有启发性的类比。