John Maynard Smith Building, School of Life Sciences, University of Sussex, Brighton, BN1 9QG, UK.
Trends Genet. 2012 Feb;28(2):78-88. doi: 10.1016/j.tig.2011.10.005. Epub 2012 Jan 16.
Current understanding of the molecular mechanisms underlying mRNA degradation indicates that specific mRNA degradation rates are primarily encoded within the mRNA message itself in the form of cis-regulatory elements bearing particular primary sequences and/or secondary-structures. Such control elements are operated by RNA-binding proteins (RBPs) and/or miRNA-containing complexes. Based on the large number of RBPs and miRNAs encoded in metazoan genomes, their complex developmental expression and that specific RBP and miRNA interactions with mRNAs can lead to distinct degradation rates, I propose that developmental gene expression is shaped by a complex 'mRNA degradation code' with high information capacity. Localised cellular events involving the modification of RBP and/or miRNA target sequences in mRNAs by alternative polyadenylation added to the activation of specific RBP and miRNA activities via cell signalling are predicted to further expand the capacity of the mRNA degradation code by coupling it to dynamic events experienced by cells at specific spatiotemporal coordinates within the developing embryo.
目前对 mRNA 降解的分子机制的理解表明,特定的 mRNA 降解速率主要由 mRNA 信息本身内部的顺式调控元件决定,这些元件带有特定的一级序列和/或二级结构。这种控制元件由 RNA 结合蛋白 (RBP) 和/或含有 miRNA 的复合物来操作。基于真核生物基因组中编码的大量 RBP 和 miRNA,它们复杂的发育表达以及特定的 RBP 和 miRNA 与 mRNAs 的相互作用可以导致不同的降解速率,我提出发育基因表达是由具有高信息容量的复杂“mRNA 降解码”塑造的。局部细胞事件涉及通过细胞信号转导激活特定的 RBP 和 miRNA 活性,同时通过添加可变多聚腺苷酸化对 RBP 和/或 miRNA 靶序列进行修饰,预计通过将其与胚胎发育过程中特定时空坐标处的细胞经历的动态事件偶联,进一步扩展 mRNA 降解码的容量。