Schmid C W
Section of Molecular and Cellular Biology and Department of Chemistry, University of California at Davis, Davis, CA 95616, USA.
Nucleic Acids Res. 1998 Oct 15;26(20):4541-50. doi: 10.1093/nar/26.20.4541.
The evolution, mobility and deleterious genetic effects of human Alus are fairly well understood. The complexity of regulated transcriptional expression of Alus is becoming apparent and insight into the mechanism of retrotransposition is emerging. Unresolved questions concern why mobile, highly repetitive short interspersed elements (SINEs) have been tolerated throughout evolution and why and how families of such sequences are periodically replaced. Either certain SINEs are more successful genomic parasites or positive selection drives their relative success and genomic maintenance. A complete understanding of the evolutionary dynamics and significance of SINEs requires determining whether or not they have a function(s). Recent evidence suggests two possibilities, one concerning DNA and the other RNA. Dispersed Alus exhibit remarkable tissue-specific differences in the level of their 5-methylcytosine content. Differences in Alu methylation in the male and female germlines suggest that Alu DNA may be involved in either the unique chromatin organization of sperm or signaling events in the early embryo. Alu RNA is increased by cellular insults and stimulates protein synthesis by inhibiting PKR, the eIF2 kinase that is regulated by double-stranded RNA. PKR serves other roles potentially linking Alu RNA to a variety of vital cell functions. Since Alus have appeared only recently within the primate lineage, this proposal provokes the challenging question of how Alu RNA could have possibly assumed a significant role in cell physiology.
人类Alu元件的进化、移动性及有害遗传效应已得到相当充分的了解。Alu元件转录表达调控的复杂性正日益显现，对逆转座机制的认识也在不断深入。尚未解决的问题包括：为何移动性的、高度重复的短散在元件（SINEs）在整个进化过程中都能被容忍，以及为何以及如何周期性地替换这类序列家族。要么某些SINEs是更成功的基因组寄生物，要么正选择推动了它们的相对成功及基因组维持。要全面理解SINEs的进化动力学及意义，需要确定它们是否具有功能。最近的证据提出了两种可能性，一种与DNA有关，另一种与RNA有关。分散的Alu元件在其5-甲基胞嘧啶含量水平上表现出显著的组织特异性差异。雄性和雌性生殖系中Alu甲基化的差异表明，Alu DNA可能参与精子独特的染色质组织或早期胚胎中的信号事件。细胞损伤会增加Alu RNA的含量，并且Alu RNA通过抑制PKR（一种受双链RNA调控的eIF2激酶）来刺激蛋白质合成。PKR还具有其他作用，可能将Alu RNA与多种重要的细胞功能联系起来。由于Alu元件直到最近才出现在灵长类谱系中，这一观点引发了一个具有挑战性的问题：Alu RNA如何可能在细胞生理学中发挥重要作用。
