TY - JOUR T1 - A frameshift mutation is repaired through nonsense-mediated gene revising in <em>E. coli</em> JF - bioRxiv DO - 10.1101/069971 SP - 069971 AU - Xiaolong Wang AU - Xuxiang Wang AU - Chunyan Li AU - Haibo Peng AU - Yalei Wang AU - Gang Chen AU - Jianye Zhang Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/19/069971.abstract N2 - The molecular mechanisms for repairing DNA damages and point mutations have been well understood but it remains unclear how a frameshift mutation is repaired. Here we report that frameshift reversion occurs in E. coli more frequently than expected and appears to be a targeted gene repair signaled by premature termination codons (PTCs), producing high-level variations in the repaired genes. Genome resequencing shows that the revertant genome is highly stable, and the single-molecule variations in the repaired genes are derived from RNA editing. A multi-omics analysis shows that the expression levels change greatly in most the DNA and RNA manipulating genes. DNA replication, transcription, RNA editing, RNA degradation, nucleotide excision repair, mismatch repair, and homologous recombination were upregulated in the frameshift or revertant, but the base excision repair was not. Moreover, genes and transposons in a duplicate region silenced in wild type E. coli were activated in the frameshift. Finally, we propose a nonsense-mediated gene revising (NMGR) model for frame repair, which also acts as a driving force for molecular evolution. In essence, nonsense mRNAs are recognized, edited, and transported to template the repair of the coding gene by RNA-directed DNA repair, nucleotide excision, mismatch repair, and homologous recombination. Thanks to NMGR, the mutation rate temporarily rises in a frameshift gene, bringing genetic diversity while repairing the frameshift mutation and accelerating the evolution process without a high mutation rate in the genome.Competing Interest StatementThe authors have declared no competing interest. ER -