Transcription attenuation associated with bacterial repetitive extragenic BIME elements

Abstract

Transcription attenuation comprises several processes that affect transcript elongation and transcription termination, and has an important role in regulating gene expression. In most cases, transcription attenuation is used as a regulatory mechanism that allows the cell to adjust protein synthesis levels in response to a specific signal. Here, by using a tRNA gene as a transcriptional reporter, we characterize a new type of transcription attenuation mechanism in Escherichia coli that involves bacterial interspersed mosaic elements (BIMEs), the main family of repetitive extragenic elements. The transcription termination factor Rho is required for attenuation in association with BIMEs, thus revealing a new role for Rho as a BIMEs-dependent global regulator of gene expression. By mutational analyses, we identified nucleotide determinants of BIMEs that are required for attenuation and showed that this process relies on a sequence-specific mechanism. Our data are consistent with a model in which BIMEs provoke a pause in RNA polymerase movement and Rho acts ultimately to terminate transcription. BIME-dependent transcription attenuation may be used as a means to differentially regulate expression of adjacent genes belonging to a single operon. BIMEs are dispersed in more than 250 operons such that attenuation can simultaneously affect expression of a large number of genes encoding unrelated proteins. This attenuation phenomenon, together with the known ability of BIMEs to stabilize upstream mRNA, reveals how dispersion of these abundant repetitive elements may affect gene regulation at the genome level.