Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Sci Rep. 2020 Dec 17;10(1):22136. doi: 10.1038/s41598-020-79197-y.
Long interspersed element 1 (LINE-1, or L1) is a retrotransposon that constitutes ~ 17% of the human genome. Although ~ 6000 full-length L1s spread throughout the human genome, their biological significance remains undetermined. The L1 5' untranslated region has bidirectional promoter activity with a sense promoter driving L1 mRNA production and an antisense promoter (ASP) driving the production of L1-gene chimeric RNAs. Here, we stimulated L1 ASP activity using CRISPR-Cas9 technology to evaluate its biological impacts. Activation of the L1 ASP upregulated the expression of L1 ASP-driven ORF0 and enhanced cell growth. Furthermore, the exogenous expression of ORF0 also enhanced cell growth. These results indicate that activation of L1 ASP activity fuels cell growth at least through ORF0 expression. To our knowledge, this is the first report demonstrating the role of the L1 ASP in a biological context. Considering that L1 sequences are desilenced in various tumor cells, our results indicate that activation of the L1 ASP may be a cause of tumor growth; therefore, interfering with L1 ASP activity may be a potential strategy to suppress the growth.
长散布元件 1（LINE-1，或 L1）是一种逆转录转座子，构成人类基因组的约 17%。尽管有~6000 个全长 L1 散布在人类基因组中，但它们的生物学意义仍未确定。L1 的 5'非翻译区具有双向启动子活性，一个有意义的启动子驱动 L1 mRNA 的产生，一个反义启动子（ASP）驱动 L1 基因嵌合 RNA 的产生。在这里，我们使用 CRISPR-Cas9 技术刺激 L1 ASP 活性，以评估其生物学影响。激活 L1 ASP 上调了 L1 ASP 驱动的 ORF0 的表达，并增强了细胞生长。此外，ORF0 的外源性表达也增强了细胞生长。这些结果表明，激活 L1 ASP 活性至少通过 ORF0 表达来促进细胞生长。据我们所知，这是第一个证明 L1 ASP 在生物学背景下作用的报告。考虑到 L1 序列在各种肿瘤细胞中去沉默，我们的结果表明，激活 L1 ASP 可能是肿瘤生长的原因；因此，干扰 L1 ASP 活性可能是抑制生长的一种潜在策略。
