Transcription fidelity: New paradigms in epigenetic inheritance, genome instability and disease

Abstract

RNA transcription errors are transient, yet frequent, events that do have consequences for the cell. However, until recently we lacked the tools to empirically measure and study these errors. Advances in RNA library preparation and next generation sequencing (NGS) have allowed the spectrum of transcription errors to be empirically measured over the entire transcriptome and in nascent transcripts. Combining these powerful methods with forward and reverse genetic strategies has refined our understanding of transcription factors known to enhance RNA accuracy and will enable the discovery of new candidates. Furthermore, these approaches will shed additional light on the complex interplay between transcription fidelity and other DNA transactions, such as replication and repair, and explore a role for transcription errors in cellular evolution and disease.

Keywords: Backtracked RNA polymerase; DNA break repair; DNA resection; DksA; Epimutation; Genetic noise; Genomic integrity; GreA; GreB; Non-genetic phenotypic heterogeneity; TFIIS; Transcription error; Transcription factor; Transcription fidelity.