Activation of LINE-1 antisense promoter stimulates the growth of cultured cells

Long interspersed element 1 (LINE-1, or L1) is a retrotransposon that constitutes ~17% of the human genome. Although ~6,000 full-length L1s spread throughout the human genome, their biological significance remains undetermined. L1 5' untranslated region has a bidirectional promoter activity with a sense promoter, driving L1 mRNA, and an antisense promoter (ASP), driving L1-gene chimeric RNAs. Here, we stimulated L1 ASP activity using the CRISPR-Cas9 system to evaluate its biological impacts. Activation of L1 ASP enhances L1 retrotransposition and cell growth. Conversely, we identified epigallocatechin gallate (EGCG) as an inhibitor of L1 ASP. The inhibition of L1 ASP by EGCG decreased cell growth but did not affect L1 retrotransposition. Collectively, these results indicate that activation of L1 ASP activity fuels cell growth. To our knowledge, this is the first report demonstrating the role of L1 ASP in the biological process. Considering that L1 sequences are de-silenced in various tumor cells, activation of L1 ASP may be a cause of tumor growth and interfering with L1 ASP activity will be a potential strategy to suppress the growth. Overall design: We compared transcriptome of cells co-expressed dCas9-VP64 with Mock (Control), sgL1ASP #1 (sg1), or #3 (sg3).