Cervantes-Ayalc Andrea, Ruiz Esparza-Garrido Ruth, Velázquez-Flores Miguel Ángel
Laboratorio de RNAs no codificantes, Unidad de Investigación Médica en Genética Humana del Hospital de Pediatría "Silvestre Frenk Freund", Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), CDMX 06720, México.
Catedrática CONACyT, Laboratorio de RNAs no codificantes, Unidad de Investigación Médica en Genética Humana del Hospital de Pediatría "Silvestre Frenk Freund", Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), CDMX 06720, México; Laboratorio de RNAs no codificantes, Unidad de Investigación Médica en Genética Humana del Hospital de Pediatría "Silvestre Frenk Freund", Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), CDMX 06720, México.
Cancer Genet. 2020 Feb;241:1-11. doi: 10.1016/j.cancergen.2019.11.004. Epub 2019 Nov 21.
Long interspersed nuclear elements 1 (LINE1) are non-LTR retrotransposons that represent the greatest remodeling force of the human genome during evolution. Genomically, LINE1 are constituted by a 5´ untranslated region (UTR), where the promoter regions are located, three open reading frames (ORF0, ORF1, and ORF2) and one 3´UTR, which has a poly(A) tail that harbors the short interspersed nuclear elements (SINEs) Alu and SVA. Although the intrinsic nature of LINE1 is to be copied and inserted into the genome, an increase in their mobility produces genomic instability. In response to this, the cell has "designed" many mechanisms controlling the retrotransposition levels of LINE1; however, alterations in these regulation systems can increase LINE1 mobility and the formation of chimeric genes. Evidence indicates that 988 human genes have LINE1 inserted in their sequence, resulting in the transcriptional control of genes by their own promoters, as well as by the LINE1 antisense promoter (ASP). To date, very little is known about the biologic impact of this and the L1-MET chimera is a more or less studied case. ASP hypomethylation has been observed in all studied cancer types, leading to increased L1-MET expression. In specific types of cancer, this L1-MET increase controls both low and high MET protein levels. It remains to be clarified if this protein product is a chimeric protein.
长散在核元件1（LINE1）是非长末端重复逆转座子，在进化过程中是人类基因组最大的重塑力量。在基因组中，LINE1由一个5´非翻译区（UTR）（启动子区域位于此处）、三个开放阅读框（ORF0、ORF1和ORF2）以及一个3´UTR组成，该3´UTR有一个带有短散在核元件（SINEs）Alu和SVA的聚腺苷酸尾巴。尽管LINE1的内在本质是被复制并插入基因组，但它们移动性的增加会导致基因组不稳定。对此，细胞“设计”了许多控制LINE1逆转座水平的机制；然而，这些调控系统的改变会增加LINE1的移动性以及嵌合基因的形成。有证据表明，988个人类基因的序列中插入了LINE1，导致基因受到自身启动子以及LINE1反义启动子（ASP）的转录控制。迄今为止，对此的生物学影响知之甚少，而L1-MET嵌合体是一个研究或多或少的案例。在所有研究的癌症类型中都观察到了ASP低甲基化，导致L1-MET表达增加。在特定类型的癌症中，这种L1-MET的增加控制着低水平和高水平的MET蛋白。该蛋白质产物是否为嵌合蛋白仍有待阐明。
