TY - JOUR T1 - Premature termination codons signaled targeted repair of frameshift mutation by endogenous RNA-directed gene editing JF - bioRxiv DO - 10.1101/069971 SP - 069971 AU - Xiaolong Wang AU - Haibo Peng AU - Chunyan Li AU - Xuxiang Wang AU - Yalei Wang AU - Gang Chen AU - Jianye Zhang Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/11/23/069971.abstract N2 - It has been presumed that most frameshifted protein coding genes yield truncated, non-functional, and may cause genetic diseases. 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. If the premature termination codons (PTCs) were changed all into sense codons, the frameshift gene was expressed without repairing, proved that in the nonsense mRNAs it is the PTCs that signaled the identification and repair of the frameshift mutation. 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): by 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, and change our perspective on molecular evolution, genetics and gene engineering. ER -