At present, the mechanism for the identification and repair of frameshift mutation is unknown at the molecular level. Here we report that in E. coli a frameshift mutation was repaired spontaneously in a precisely targeted manner. Genome resequencing showed that the revertants′ genome is not more variable than the wild-type genome, while transcriptome analysis showed that genes, proteins and pathways for RNA editing, mismatch repair and homologous recombination were upregulated. We proposed a new model for autonomous gene repair, RNA-directed Gene Editing (RdGE): in mRNA surveillance the nonsense mRNAs were recognized through PTC signaling, edited and used to direct the repair of the faulty coding DNA sequence. The RdGE pathway is highly conserved among species, which may revise our view on central dogma, change our perspective on molecular evolution and genetic engineering.