Cross-domain signal grammars of transcription termination.

Abstract

Transcription termination establishes gene boundaries, recycles RNA polymerase, and prevents interference between neighboring transcription units. Termination depends on cis-acting elements, trans-acting factors, and the susceptibility of the elongation complex to pausing, cleavage, destabilization, or release. Predicted motifs, stable RNA ends, processing sites, readthrough regions, and polymerase-release regions are nevertheless often treated as measurements of the same event, which complicates mechanistic comparison and model development. This review compares termination signals as context-dependent rule systems in which sequence determinants, RNA structure and accessibility, and processing sites are interpreted through their order and spacing, molecular readers, conditional gates, and kinetic windows. It examines bacterial intrinsic and Rho-dependent termination, archaeal U-rich and cleavage-linked routes, PAS-centered RNAPII termination, and nuclear Pol I, Pol III, and specialized RNAPII pathways, showing how shared kinetic constraints are met by divergent molecular solutions shaped by cellular organization. Matching each signal feature to the measurement that supports it clarifies cross-domain comparisons and guides transcriptome-wide analysis, prediction, and terminator engineering in defined biological systems.