Conditional termination of transcription is shaped by Rho and translated uORFS inMycobacterium tuberculosis

Abstract

SUMMARYLittle is known about the decisions behind transcription elongationversustermination in the human pathogenMycobacterium tuberculosis. By applying Term-seq toM. tuberculosiswe found that the majority of transcription termination is premature and associated with translated regions, i.e. within previously annotated or newly identified open reading frames. Computational predictions and Term-seq analysis upon depletion of termination factor Rho suggests that Rho-dependent transcription termination dominates all TTS including those associated with regulatory 5’ leaders. Moreover, our results suggest that tightly coupled translation, in the form of overlapping stop and start codons, may suppress Rho-dependent termination. This study provides detailed insights into novelM. tuberculosis cis-regulatory elements, where Rho-dependent, conditional termination of transcription and translational coupling together play major roles in gene expression control. Our findings contribute to a deeper understanding of the fundamental regulatory mechanisms that enableM. tuberculosisadaptation to the host environment offering novel potential points of intervention.