Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane University Cancer Center and Tulane Center for Aging.
Front Biosci (Landmark Ed). 2012 Jan 1;17(4):1329-44. doi: 10.2741/3990.
Historically the accumulated mass of mammalian transposable elements (TEs), particularly those located within gene boundaries, was viewed as a genetic burden potentially detrimental to the genomic landscape. This notion has been strengthened by the discovery that transposable sequences can alter the architecture of the transcriptome, not only through insertion, but also long after the integration process is completed. Insertions previously considered harmless are now known to impact the expression of host genes via modification of the transcript quality or quantity, transcriptional interference, or by the control of pathways that affect the mRNA life-cycle. Conversely, several examples of the evolutionary advantageous impact of TEs on the host gene structure that diversified the cellular transcriptome are reported. TE-induced changes in gene expression can be tissue- or disease-specific, raising the possibility that the impact of TE sequences may vary during development, among normal cell types, and between normal and disease-affected tissues. The understanding of the rules and abundance of TE-interference with gene expression is in its infancy, and its contribution to human disease and/or evolution remains largely unexplored.
从历史上看,哺乳动物转座元件(TEs)的积累质量,特别是那些位于基因边界内的转座元件,被视为一种潜在的遗传负担,可能对基因组景观有害。这一观点得到了加强,因为发现转座序列不仅可以通过插入,而且在整合过程完成很久之后,改变转录组的结构。以前被认为是无害的插入现在被认为会通过改变转录本的质量或数量、转录干扰,或者通过控制影响 mRNA 生命周期的途径来影响宿主基因的表达。相反,据报道,TE 对宿主基因结构的进化有利影响的几个例子使细胞转录组多样化。TE 诱导的基因表达变化可能具有组织或疾病特异性,这增加了 TE 序列在发育过程中、在正常细胞类型之间以及在正常组织和受疾病影响的组织之间可能存在差异的可能性。对 TE 干扰基因表达的规则和丰度的理解还处于起步阶段,其对人类疾病和/或进化的贡献在很大程度上仍未得到探索。