Tufarelli Cristina, Cruickshanks Hazel A, Meehan Richard R
School of Medicine; University of Nottingham; Royal Derby Hospital Centre; Derby, England UK ; Centre for Genetics and Genomics; University of Nottingham; Nottingham, England UK.
Mob Genet Elements. 2013 Sep 1;3(5):e26832. doi: 10.4161/mge.26832. Epub 2013 Oct 25.
The ability of active retrotransposon elements to move within the host genome and alter gene expression with subsequent phenotypic variation led to their initial discovery. In recent years it has become apparent that these elements can also modulate host gene expression independently of their transposition activity. Many retrotransposons maintain endogenous promoter motifs that can potentially drive expression of adjacent DNA modules. Similarly to transposition dependent dysregulation, these proto-promoters can progress disease states when active. Indeed aberrant activation of retrotransposon derived promoters in cancer can lead to transcription of oncogenic isoforms of cellular genes. Here we propose that activation of promoters of transposable elements in cancer can also drive transcription of long non-coding RNAs whose expression leads to silencing of linked tumor suppressor genes. Such transcription driven by aberrantly active transposable elements in cancer can lead to a characteristic reprogramming of epigenetic profiles, thus extending the potential molecular mechanisms whereby retrotransposons can directly contribute to cancer development and subsequent progression.
活性逆转录转座子元件在宿主基因组内移动并通过随后的表型变异改变基因表达的能力导致了它们的最初发现。近年来，很明显这些元件也可以独立于其转座活性来调节宿主基因表达。许多逆转录转座子保留了内源性启动子基序，这些基序可能驱动相邻DNA模块的表达。与依赖转座的失调类似，这些原启动子在激活时可导致疾病状态进展。事实上，癌症中逆转录转座子衍生启动子的异常激活可导致细胞基因致癌异构体的转录。在此我们提出，癌症中转座元件启动子的激活也可驱动长链非编码RNA的转录，其表达导致相关肿瘤抑制基因的沉默。癌症中异常活跃的转座元件驱动的这种转录可导致表观遗传谱的特征性重编程，从而扩展了逆转录转座子可直接促进癌症发展及后续进展的潜在分子机制。
