RNA-mediated gene fusion in mammalian cells

Significance This report provides striking evidence that expression of a chimeric RNA mimicking a fusion RNA can drive the formation of gene fusions in mammalian cells. However, it is the antisense rather than sense chimeric RNAs that effectively drive gene fusion. The discovery that the cellular AZI1 RNA, not AZI1 protein, can act as an “initiator” RNA to induce TMPRSS2–ERG gene fusion indicates that this mechanism may have important biological relevance to oncogenesis. RNA-mediated gene fusion, a mechanism that relies on sequence-specific interactions, can account for the “specificity” of genes that were selected to undergo gene fusion. The results could also have fundamental implications in mammalian genome stability, as well as gene-editing technology via mechanisms native to mammalian cells.