Agenda

RNA transcription is a central control point for gene expression in the cell. Recent single-molecule experiments show that both RNA transcription and DNA replication are highly irregular processes, exhibiting long pauses and direction reversals. While the origin and functional significance of irregular dynamics in transcription remains
controversial, much of the complex dynamics seen during replication is recognized as stemming from a sophisticated proofreading mechanism that lowers the error content of the final product. By crucially extending established theoretical proofreading schemes to account for the observed transcript shortening, we show that irregular transcription dynamics does not predominantly rely on sequence heterogeneity as previously assumed. In particular, striking a balance between the competing demands of proofreading, nucleotide consumption and transcription speed, we reveal a counter intuitive mechanism whereby slow and irregular transcription at the level of individual polymerases results in astronomical gains in the rate with which long
and error-free transcripts can be produced.